rs1480934889

Variant names:

• chrX-101277702-C-T
• rs1480934889
• NM_001168474.2:c.595G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001168474.2(TAF7L):​c.595G>A​(p.Glu199Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000913 in 109,508 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000091 (0 hom., 0 hem., cov: 21)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: TAF7L NM_001168474.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.70
• Publications: 0 publications found

Genes affected

TAF7L (HGNC:11548): (TATA-box binding protein associated factor 7 like) This gene is similar to a mouse gene that encodes a TATA box binding protein-associated factor, and shows testis-specific expression. The encoded protein could be a spermatogenesis-specific component of the DNA-binding general transcription factor complex TFIID. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168474.2. 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
	TAF7L	NM_001168474.2	MANE Select	c.595G>A	p.Glu199Lys	missense	Exon 9 of 13	NP_001161946.1	Q5H9L4-2
	TAF7L	NM_024885.4		c.853G>A	p.Glu285Lys	missense	Exon 9 of 13	NP_079161.3	Q5H9L4-1
	TAF7L	NM_001410720.1		c.595G>A	p.Glu199Lys	missense	Exon 9 of 12	NP_001397649.1	Q5H9L4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF7L	ENST00000356784.2	TSL:1 MANE Select	c.595G>A	p.Glu199Lys	missense	Exon 9 of 13	ENSP00000349235.1	Q5H9L4-2
	TAF7L	ENST00000372907.7	TSL:1	c.853G>A	p.Glu285Lys	missense	Exon 9 of 13	ENSP00000361998.3	Q5H9L4-1
	TAF7L	ENST00000324762.10	TSL:2	c.595G>A	p.Glu199Lys	missense	Exon 8 of 11	ENSP00000320283.6	Q5H9L4-3

Frequencies

GnomAD3 genomes AF: 0.00000913 AC: 1 AN: 109508 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.0000332

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1085370 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 351894

African (AFR) AF: 0.00 AC: 0 AN: 25921

American (AMR) AF: 0.00 AC: 0 AN: 33570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19138

East Asian (EAS) AF: 0.00 AC: 0 AN: 29921

South Asian (SAS) AF: 0.00 AC: 0 AN: 52437

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40425

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4051

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 834251

Other (OTH) AF: 0.00 AC: 0 AN: 45656

GnomAD4 genome AF: 0.00000913 AC: 1 AN: 109508 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 31780

African (AFR) AF: 0.0000332 AC: 1 AN: 30095

American (AMR) AF: 0.00 AC: 0 AN: 10068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2627

East Asian (EAS) AF: 0.00 AC: 0 AN: 3517

South Asian (SAS) AF: 0.00 AC: 0 AN: 2537

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52776

Other (OTH) AF: 0.00 AC: 0 AN: 1458

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.7
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.27
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.028	D
Polyphen		0.99	D
Vest4		0.43
MutPred		0.45		Gain of ubiquitination at E285 (P = 0.0121)
MVP		0.27
MPC		0.92
ClinPred		0.94	D
GERP RS		5.3
Varity_R		0.43
gMVP		0.34
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: 17

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

Other links and lift over

dbSNP: rs1480934889; hg19: chrX-100532690;