18-26227252-C-T

Variant names:

• chr18-26227252-C-T
• rs986737217
• NM_005640.3:c.319C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005640.3(TAF4B):​c.319C>T​(p.Pro107Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TAF4B NM_005640.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27

Genes affected

TAF4B (HGNC:11538): (TATA-box binding protein associated factor 4b) TATA binding protein (TBP) and TBP-associated factors (TAFs) participate in the formation of the TFIID protein complex, which is involved in initiation of transcription of genes by RNA polymerase II. This gene encodes a cell type-specific TAF that may be responsible for mediating transcription by a subset of activators in B cells. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2887931).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF4B	NM_005640.3	c.319C>T	p.Pro107Ser	missense_variant	Exon 1 of 15	ENST00000269142.10	NP_005631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF4B	ENST00000269142.10	c.319C>T	p.Pro107Ser	missense_variant	Exon 1 of 15	1	NM_005640.3	ENSP00000269142.6
TAF4B	ENST00000578121.5	c.319C>T	p.Pro107Ser	missense_variant	Exon 1 of 15	2		ENSP00000462980.1
TAF4B	ENST00000418698.3	n.319C>T		non_coding_transcript_exon_variant	Exon 1 of 16	5		ENSP00000389365.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460892 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726750

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.31	T;T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.6	D;.
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.54	P;.
Vest4		0.44
MutPred		0.37		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.19
MPC		1.9
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.44
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs986737217; hg19: chr18-23807216;