rs3810715

Variant names:

• chrX-151716148-C-T
• rs3810715
• NM_033085.3:c.29C>T

Variant summary

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

The NM_033085.3(FATE1):​c.29C>T​(p.Ala10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,165,186 control chromosomes in the GnomAD database, including 6,576 homozygotes. There are 45,885 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (613 hom., 3675 hem., cov: 23)
  • Exomes 𝑓: 0.12 (5963 hom. 42210 hem.)
• Consequence: FATE1 NM_033085.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 10 publications found

Genes affected

FATE1 (HGNC:24683): (fetal and adult testis expressed 1) This gene encodes a cancer-testis antigen that is highly expressed in hepatocellular carcinomas and other tumors and weakly expressed in normal tissues except testis. The protein is strongly expressed in spermatogonia, primary spermatocytes, and Sertoli cells in seminiferous tubules. This protein may have a role in the control of early testicular differentiation and cell proliferation. [provided by RefSeq, Jan 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048240423).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FATE1	NM_033085.3	c.29C>T	p.Ala10Val	missense_variant	Exon 1 of 5	ENST00000370350.7	NP_149076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FATE1	ENST00000370350.7	c.29C>T	p.Ala10Val	missense_variant	Exon 1 of 5	1	NM_033085.3	ENSP00000359375.3
FATE1	ENST00000417321.1	c.5C>T	p.Ala2Val	missense_variant	Exon 1 of 4	3		ENSP00000400493.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 12442 AN: 111687 Hom.: 612 Cov.: 23

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.0503

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.109

GnomAD2 exomes AF: 0.126 AC: 14394 AN: 114430 AF XY: 0.118

Gnomad AFR exome AF: 0.0580

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.268

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.125 AC: 131614 AN: 1053446 Hom.: 5963 Cov.: 30 AF XY: 0.123 AC XY: 42210 AN XY: 344380

African (AFR) AF: 0.0601 AC: 1498 AN: 24909

American (AMR) AF: 0.101 AC: 2828 AN: 27877

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 2655 AN: 18628

East Asian (EAS) AF: 0.246 AC: 6664 AN: 27104

South Asian (SAS) AF: 0.0513 AC: 2549 AN: 49717

European-Finnish (FIN) AF: 0.163 AC: 6114 AN: 37621

Middle Eastern (MID) AF: 0.129 AC: 521 AN: 4051

European-Non Finnish (NFE) AF: 0.126 AC: 103181 AN: 819189

Other (OTH) AF: 0.126 AC: 5604 AN: 44350

GnomAD4 genome AF: 0.111 AC: 12449 AN: 111740 Hom.: 613 Cov.: 23 AF XY: 0.108 AC XY: 3675 AN XY: 33956

African (AFR) AF: 0.0617 AC: 1900 AN: 30779

American (AMR) AF: 0.110 AC: 1172 AN: 10635

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 377 AN: 2643

East Asian (EAS) AF: 0.244 AC: 852 AN: 3496

South Asian (SAS) AF: 0.0505 AC: 133 AN: 2635

European-Finnish (FIN) AF: 0.157 AC: 953 AN: 6085

Middle Eastern (MID) AF: 0.157 AC: 34 AN: 216

European-Non Finnish (NFE) AF: 0.127 AC: 6713 AN: 53052

Other (OTH) AF: 0.108 AC: 165 AN: 1523

Alfa AF: 0.128 Hom.: 8574

Bravo AF: 0.111

TwinsUK AF: 0.119 AC: 441

ALSPAC AF: 0.124 AC: 359

ESP6500AA AF: 0.0541 AC: 194

ESP6500EA AF: 0.107 AC: 641

ExAC AF: 0.0516 AC: 2625

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.0
DANN	Benign	0.38
DEOGEN2	Benign	0.012	T;T
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.41	T;T
MetaRNN	Benign	0.0048	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.
PhyloP100		1.4
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.084
Sift	Benign	0.24	T;T
Sift4G	Uncertain	0.038	D;T
Polyphen		0.77	P;.
Vest4		0.013
MPC		0.021
ClinPred		0.0081	T
GERP RS		3.0
PromoterAI		-0.11	Neutral
Varity_R		0.042
gMVP		0.065
Mutation Taster		=93/7	polymorphism (auto)

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: rs3810715; hg19: chrX-150884620; COSMIC: COSV64848886;