rs5951328

Positions:

• chrX-101292945-A-G
• chrX-101292945-A-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The ENST00000372907.7(TAF7L):​c.101T>C​(p.Leu34Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.99 (38178 hom., 30539 hem., cov: 21)
  • Exomes 𝑓: 0.99 (356626 hom. 358515 hem.)
  • Failed GnomAD Quality Control
• Consequence: TAF7L ENST00000372907.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.402261E-6).
• BP6: Variant X-101292945-A-G is Benign according to our data. Variant chrX-101292945-A-G is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF7L	NM_024885.4	c.101T>C	p.Leu34Pro	missense_variant	1/13
TAF7L	XM_006724664.2	c.101T>C	p.Leu34Pro	missense_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF7L	ENST00000372907.7	c.101T>C	p.Leu34Pro	missense_variant	1/13	1		P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 107526 AN: 108494 Hom.: 38182 Cov.: 21 AF XY: 0.992 AC XY: 30473 AN XY: 30732 FAILED QC

Gnomad AFR AF: 0.998

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.993

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.994

GnomAD3 exomes AF: 0.991 AC: 181518 AN: 183187 Hom.: 56665 AF XY: 0.991 AC XY: 67158 AN XY: 67773

Gnomad AFR exome AF: 0.998

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 0.997

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.994

Gnomad FIN exome AF: 0.985

Gnomad NFE exome AF: 0.986

Gnomad OTH exome AF: 0.989

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.986 AC: 1082358 AN: 1098208 Hom.: 356626 Cov.: 59 AF XY: 0.986 AC XY: 358515 AN XY: 363570

Gnomad4 AFR exome AF: 0.999

Gnomad4 AMR exome AF: 0.997

Gnomad4 ASJ exome AF: 0.996

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.994

Gnomad4 FIN exome AF: 0.984

Gnomad4 NFE exome AF: 0.983

Gnomad4 OTH exome AF: 0.988

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.991 AC: 107583 AN: 108550 Hom.: 38178 Cov.: 21 AF XY: 0.992 AC XY: 30539 AN XY: 30798

Gnomad4 AFR AF: 0.998

Gnomad4 AMR AF: 0.997

Gnomad4 ASJ AF: 0.998

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.993

Gnomad4 FIN AF: 0.986

Gnomad4 NFE AF: 0.986

Gnomad4 OTH AF: 0.995

Alfa AF: 0.987 Hom.: 93015

Bravo AF: 0.993

TwinsUK AF: 0.987 AC: 3660

ALSPAC AF: 0.979 AC: 2829

ESP6500AA AF: 0.997 AC: 3824

ESP6500EA AF: 0.989 AC: 6651

ExAC AF: 0.990 AC: 120231

EpiCase AF: 0.990

EpiControl AF: 0.987

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-1.0	T
BayesDel_noAF	Benign	-1.2
CADD	Benign	0.12
DANN	Benign	0.37
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.34	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.21	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.034
Sift	Benign	0.91	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.0080
MPC		0.43
ClinPred		0.0021	T
GERP RS		-2.8
Varity_R		0.045
gMVP		0.093

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

Other links and lift over

dbSNP: rs5951328; hg19: chrX-100547933;