rs2492937

Variant names:

• chr6-42086608-G-A
• rs2492937
• ENST00000456846.6:c.921-111G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001438580.1(TAF8):​c.*26-111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,063,322 control chromosomes in the GnomAD database, including 26,731 homozygotes. 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: 𝑓 0.28 (8968 hom., cov: 32)
  • Exomes 𝑓: 0.18 (17763 hom.)
• Consequence: TAF8 NM_001438580.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438580.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF8	NM_001438580.1		c.*26-111G>A		intron	N/A	NP_001425509.1
	TAF8	NM_001410907.1		c.921-111G>A		intron	N/A	NP_001397836.1	Q7Z7C8-2
	TAF8	NM_001438582.1		c.630-111G>A		intron	N/A	NP_001425511.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF8	ENST00000456846.6	TSL:1	c.921-111G>A		intron	N/A	ENSP00000411900.2	Q7Z7C8-2
	TAF8	ENST00000372982.8	TSL:2	c.*26-111G>A		intron	N/A	ENSP00000362073.4	Q7Z7C8-4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42732 AN: 151938 Hom.: 8940 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0929

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.181 AC: 165286 AN: 911266 Hom.: 17763 AF XY: 0.178 AC XY: 83626 AN XY: 468924

African (AFR) AF: 0.618 AC: 13632 AN: 22060

American (AMR) AF: 0.111 AC: 3877 AN: 35038

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 4158 AN: 22098

East Asian (EAS) AF: 0.104 AC: 3484 AN: 33490

South Asian (SAS) AF: 0.138 AC: 9582 AN: 69292

European-Finnish (FIN) AF: 0.143 AC: 6825 AN: 47856

Middle Eastern (MID) AF: 0.182 AC: 867 AN: 4772

European-Non Finnish (NFE) AF: 0.180 AC: 114417 AN: 634516

Other (OTH) AF: 0.200 AC: 8444 AN: 42144

GnomAD4 genome AF: 0.282 AC: 42808 AN: 152056 Hom.: 8968 Cov.: 32 AF XY: 0.274 AC XY: 20355 AN XY: 74346

African (AFR) AF: 0.595 AC: 24657 AN: 41448

American (AMR) AF: 0.154 AC: 2361 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3468

East Asian (EAS) AF: 0.0927 AC: 479 AN: 5166

South Asian (SAS) AF: 0.122 AC: 591 AN: 4826

European-Finnish (FIN) AF: 0.132 AC: 1397 AN: 10594

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11925 AN: 67960

Other (OTH) AF: 0.249 AC: 524 AN: 2108

Alfa AF: 0.217 Hom.: 13552

Bravo AF: 0.299

Asia WGS AF: 0.121 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2492937; hg19: chr6-42054346;