Variant 6-42056011-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_138572.3(TAF8):c.361G>T(p.Ala121Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)

Consequence

TAF8
NM_138572.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.50

Variant links:

Genes affected

TAF8 (HGNC:17300): (TATA-box binding protein associated factor 8) This gene encodes one of several TATA-binding protein (TBP)-associated factors (TAFs), which are integral subunits of the general transcription factor complex TFIID. TFIID recognizes the core promoter of many genes and nucleates the assembly of a transcription preinitiation complex containing RNA polymerase II and other initiation factors. The protein encoded by this gene contains an H4-like histone fold domain, and interacts with several subunits of TFIID including TBP and the histone-fold protein TAF10. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

TAF8 links:

TAF8 (HGNC:):

TAF8 links:

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ACMG classification

Classification made for transcript

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=0.37195054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF8	NM_138572.3 linkuse as main transcript	c.361G>T	p.Ala121Ser	missense_variant	4/9	ENST00000372977.8	NP_612639.2	Q7Z7C8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF8	ENST00000372977.8 linkuse as main transcript	c.361G>T	p.Ala121Ser	missense_variant	4/9	1	NM_138572.3	ENSP00000362068.3		Q7Z7C8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.361G>T (p.A121S) alteration is located in exon 4 (coding exon 4) of the TAF8 gene. This alteration results from a G to T substitution at nucleotide position 361, causing the alanine (A) at amino acid position 121 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;.;.;.;T;T;.;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

D;.;D;D;T;D;D;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.36

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.1

.;M;M;M;.;M;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.59

N;N;N;N;N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.24

T;.;T;.;T;T;T;T

Sift4G

Benign

0.18

T;T;T;T;D;T;T;D

Polyphen

0.50, 0.99, 1.0, 0.99, 0.19

.;P;D;P;D;D;B;.

Vest4

0.72

MutPred

0.46

Gain of glycosylation at A121 (P = 0.0085);Gain of glycosylation at A121 (P = 0.0085);Gain of glycosylation at A121 (P = 0.0085);Gain of glycosylation at A121 (P = 0.0085);Gain of glycosylation at A121 (P = 0.0085);Gain of glycosylation at A121 (P = 0.0085);.;.;

MVP

0.30

MPC

0.80

ClinPred

0.81

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.42

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over