rs398124656

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3

The NM_003184.4(TAF2):​c.557C>T​(p.Thr186Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

TAF2
NM_003184.4 missense

Scores

6
7
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.95
Variant links:
Genes affected
TAF2 (HGNC:11536): (TATA-box binding protein associated factor 2) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes one of the larger subunits of TFIID that is stably associated with the TFIID complex. It contributes to interactions at and downstream of the transcription initiation site, interactions that help determine transcription complex response to activators. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TAF2. . Gene score misZ 2.7836 (greater than the threshold 3.09). Trascript score misZ 3.5113 (greater than threshold 3.09). GenCC has associacion of gene with microcephaly-thin corpus callosum-intellectual disability syndrome.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TAF2NM_003184.4 linkuse as main transcriptc.557C>T p.Thr186Ile missense_variant 5/26 ENST00000378164.7 NP_003175.2 Q6P1X5B3KMD8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TAF2ENST00000378164.7 linkuse as main transcriptc.557C>T p.Thr186Ile missense_variant 5/261 NM_003184.4 ENSP00000367406.2 Q6P1X5
TAF2ENST00000686879.1 linkuse as main transcriptc.557C>T p.Thr186Ile missense_variant 5/27 ENSP00000509206.1 A0A8I5KV60
TAF2ENST00000685235.1 linkuse as main transcriptc.557C>T p.Thr186Ile missense_variant 5/26 ENSP00000510174.1 A0A8I5QJR0
TAF2ENST00000688645.1 linkuse as main transcriptc.557C>T p.Thr186Ile missense_variant 5/25 ENSP00000509978.1 A0A8I5KSY6
TAF2ENST00000523904.2 linkuse as main transcriptc.557C>T p.Thr186Ile missense_variant 5/253 ENSP00000430832.2 H0YC37
TAF2ENST00000690144.1 linkuse as main transcriptc.557C>T p.Thr186Ile missense_variant 5/26 ENSP00000510548.1 A0A8I5KUQ2
TAF2ENST00000521007.2 linkuse as main transcriptc.557C>T p.Thr186Ile missense_variant 6/73 ENSP00000428484.2 E5RI28
TAF2ENST00000685202.1 linkuse as main transcriptn.557C>T non_coding_transcript_exon_variant 5/27 ENSP00000509214.1 A0A8I5QJD7
TAF2ENST00000685503.1 linkuse as main transcriptn.557C>T non_coding_transcript_exon_variant 5/26 ENSP00000509198.1 A0A8I5KXS3
TAF2ENST00000685663.1 linkuse as main transcriptn.*429C>T non_coding_transcript_exon_variant 7/28 ENSP00000508988.1 A0A8I5KUD2
TAF2ENST00000685824.1 linkuse as main transcriptn.*372C>T non_coding_transcript_exon_variant 4/24 ENSP00000510262.1 A0A8I5KU60
TAF2ENST00000685876.1 linkuse as main transcriptn.*275C>T non_coding_transcript_exon_variant 6/27 ENSP00000510493.1 A0A8I5KUD2
TAF2ENST00000685993.1 linkuse as main transcriptn.*372C>T non_coding_transcript_exon_variant 4/25 ENSP00000510102.1 A0A8I5KU60
TAF2ENST00000686098.1 linkuse as main transcriptn.557C>T non_coding_transcript_exon_variant 5/25 ENSP00000509102.1 A0A8I5KXP3
TAF2ENST00000689164.1 linkuse as main transcriptn.557C>T non_coding_transcript_exon_variant 5/24 ENSP00000508729.1 A0A8I5KR26
TAF2ENST00000689919.1 linkuse as main transcriptn.*275C>T non_coding_transcript_exon_variant 6/26 ENSP00000510768.1 A0A8I5KUD2
TAF2ENST00000690808.1 linkuse as main transcriptn.557C>T non_coding_transcript_exon_variant 5/26 ENSP00000509791.1 A0A8I5KVC1
TAF2ENST00000690922.1 linkuse as main transcriptn.557C>T non_coding_transcript_exon_variant 5/26 ENSP00000509498.1 A0A8I5KPW0
TAF2ENST00000691880.1 linkuse as main transcriptn.*213C>T non_coding_transcript_exon_variant 4/25 ENSP00000508515.1 A0A8I5KNG3
TAF2ENST00000692518.1 linkuse as main transcriptn.*372C>T non_coding_transcript_exon_variant 4/25 ENSP00000508959.1 A0A8I5KU60
TAF2ENST00000692707.1 linkuse as main transcriptn.*275C>T non_coding_transcript_exon_variant 6/28 ENSP00000509024.1 A0A8I5KUD2
TAF2ENST00000685663.1 linkuse as main transcriptn.*429C>T 3_prime_UTR_variant 7/28 ENSP00000508988.1 A0A8I5KUD2
TAF2ENST00000685824.1 linkuse as main transcriptn.*372C>T 3_prime_UTR_variant 4/24 ENSP00000510262.1 A0A8I5KU60
TAF2ENST00000685876.1 linkuse as main transcriptn.*275C>T 3_prime_UTR_variant 6/27 ENSP00000510493.1 A0A8I5KUD2
TAF2ENST00000685993.1 linkuse as main transcriptn.*372C>T 3_prime_UTR_variant 4/25 ENSP00000510102.1 A0A8I5KU60
TAF2ENST00000689919.1 linkuse as main transcriptn.*275C>T 3_prime_UTR_variant 6/26 ENSP00000510768.1 A0A8I5KUD2
TAF2ENST00000691880.1 linkuse as main transcriptn.*213C>T 3_prime_UTR_variant 4/25 ENSP00000508515.1 A0A8I5KNG3
TAF2ENST00000692518.1 linkuse as main transcriptn.*372C>T 3_prime_UTR_variant 4/25 ENSP00000508959.1 A0A8I5KU60
TAF2ENST00000692707.1 linkuse as main transcriptn.*275C>T 3_prime_UTR_variant 6/28 ENSP00000509024.1 A0A8I5KUD2
TAF2ENST00000685684.1 linkuse as main transcriptn.520+37C>T intron_variant ENSP00000509441.1 A0A8I5KY57
TAF2ENST00000688037.1 linkuse as main transcriptn.139-1856C>T intron_variant ENSP00000510169.1 A0A8I5KRI4
TAF2ENST00000690031.1 linkuse as main transcriptn.*238+37C>T intron_variant ENSP00000508549.1 A0A8I5KUD2
TAF2ENST00000691847.1 linkuse as main transcriptn.538+19C>T intron_variant ENSP00000509663.1 A0A8I5QJJ6
TAF2ENST00000692916.1 linkuse as main transcriptn.419-1856C>T intron_variant ENSP00000509603.1 A0A8I5QJI9

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152070
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152070
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Uncertain
0.077
D
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.025
T
MetaRNN
Pathogenic
0.83
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L
PrimateAI
Pathogenic
0.90
D
PROVEAN
Uncertain
-3.2
D
REVEL
Uncertain
0.44
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.93
P
Vest4
0.85
MutPred
0.80
Gain of helix (P = 0.1736);
MVP
0.23
MPC
1.1
ClinPred
0.97
D
GERP RS
5.8
Varity_R
0.47
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs398124656; hg19: chr8-120816121; API