rs1601726416

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030573.3(THAP7):​c.736G>T​(p.Ala246Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A246T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

THAP7
NM_030573.3 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0470
Variant links:
Genes affected
THAP7 (HGNC:23190): (THAP domain containing 7) Enables several functions, including C2H2 zinc finger domain binding activity; histone binding activity; and histone deacetylase binding activity. Involved in negative regulation of histone acetylation and negative regulation of transcription by RNA polymerase II. Located in nuclear membrane and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11012089).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
THAP7NM_030573.3 linkc.736G>T p.Ala246Ser missense_variant Exon 4 of 4 ENST00000215742.9 NP_085050.2 Q9BT49
THAP7NM_001008695.1 linkc.736G>T p.Ala246Ser missense_variant Exon 5 of 5 NP_001008695.1 Q9BT49

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
THAP7ENST00000215742.9 linkc.736G>T p.Ala246Ser missense_variant Exon 4 of 4 1 NM_030573.3 ENSP00000215742.4 Q9BT49

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460454
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726550
show subpopulations
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Uncertain
0.027
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
T;T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.71
.;T
M_CAP
Uncertain
0.16
D
MetaRNN
Benign
0.11
T;T
MetaSVM
Uncertain
0.11
D
MutationAssessor
Benign
0.55
N;N
PrimateAI
Pathogenic
0.80
D
PROVEAN
Benign
-0.93
N;N
REVEL
Benign
0.22
Sift
Benign
0.10
T;T
Sift4G
Benign
0.083
T;T
Polyphen
0.26
B;B
Vest4
0.20
MutPred
0.24
Gain of phosphorylation at A246 (P = 0.0377);Gain of phosphorylation at A246 (P = 0.0377);
MVP
0.89
MPC
0.43
ClinPred
0.44
T
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.086
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs1601726416; hg19: chr22-21354363; API