10-103368396-T-G

Variant names:

• chr10-103368396-T-G
• rs2093350518
• NM_006951.5:c.407T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006951.5(TAF5):​c.407T>G​(p.Val136Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 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. V136A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000048 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000054 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAF5 NM_006951.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.652
• Publications: 0 publications found

Genes affected

TAF5 (HGNC:11539): (TATA-box binding protein associated factor 5) 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 an integral subunit of TFIID associated with all transcriptionally competent forms of that complex. This subunit interacts strongly with two TFIID subunits that show similarity to histones H3 and H4, and it may participate in forming a nucleosome-like core in the TFIID complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.052879363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF5	NM_006951.5	c.407T>G	p.Val136Gly	missense_variant	Exon 1 of 11	ENST00000369839.4	NP_008882.2
TAF5	NM_139052.3	c.407T>G	p.Val136Gly	missense_variant	Exon 1 of 10		NP_620640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF5	ENST00000369839.4	c.407T>G	p.Val136Gly	missense_variant	Exon 1 of 11	1	NM_006951.5	ENSP00000358854.3

Frequencies

GnomAD3 genomes AF: 0.0000481 AC: 7 AN: 145494 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000251

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: 0.000209

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000605

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000544 AC: 7 AN: 1287290 Hom.: 0 Cov.: 35 AF XY: 0.00000784 AC XY: 5 AN XY: 637678

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27594

American (AMR) AF: 0.0000569 AC: 2 AN: 35136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20386

East Asian (EAS) AF: 0.0000326 AC: 1 AN: 30680

South Asian (SAS) AF: 0.00 AC: 0 AN: 80396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3510

European-Non Finnish (NFE) AF: 0.00000394 AC: 4 AN: 1014036

Other (OTH) AF: 0.00 AC: 0 AN: 50216

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000481 AC: 7 AN: 145634 Hom.: 0 Cov.: 33 AF XY: 0.0000282 AC XY: 2 AN XY: 71010

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000250 AC: 1 AN: 39976

American (AMR) AF: 0.00 AC: 0 AN: 14786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.00 AC: 0 AN: 4498

South Asian (SAS) AF: 0.00 AC: 0 AN: 4068

European-Finnish (FIN) AF: 0.000209 AC: 2 AN: 9580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000605 AC: 4 AN: 66126

Other (OTH) AF: 0.00 AC: 0 AN: 2056

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.86
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.90	N
PhyloP100		0.65
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.044
Sift	Benign	0.51	T
Sift4G	Benign	0.39	T
Polyphen		0.0020	B
Vest4		0.089
MutPred		0.11		Loss of stability (P = 0.0366);
MVP		0.14
MPC		0.99
ClinPred		0.12	T
GERP RS		-1.6
PromoterAI		0.073	Neutral
Varity_R		0.043
gMVP		0.20
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs2093350518; hg19: chr10-105128153;