chrX-151716212-C-A

Variant names:

• chrX-151716212-C-A
• rs1363515397
• NM_033085.3:c.93C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_033085.3(FATE1):​c.93C>A​(p.His31Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000249 in 1,165,618 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000026 (0 hom. 12 hem.)
• Consequence: FATE1 NM_033085.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.01
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0507482).
• BS2: High Hemizygotes in GnomAdExome4 at 12 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033085.3. 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
	FATE1	NM_033085.3	MANE Select	c.93C>A	p.His31Gln	missense	Exon 1 of 5	NP_149076.1	Q969F0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FATE1	ENST00000370350.7	TSL:1 MANE Select	c.93C>A	p.His31Gln	missense	Exon 1 of 5	ENSP00000359375.3	Q969F0
	FATE1	ENST00000940339.1		c.93C>A	p.His31Gln	missense	Exon 2 of 6	ENSP00000610398.1
	FATE1	ENST00000940340.1		c.93C>A	p.His31Gln	missense	Exon 2 of 6	ENSP00000610399.1

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112378 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000872 AC: 1 AN: 114639 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000225

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000256 AC: 27 AN: 1053240 Hom.: 0 Cov.: 29 AF XY: 0.0000349 AC XY: 12 AN XY: 344048

African (AFR) AF: 0.00 AC: 0 AN: 24890

American (AMR) AF: 0.00 AC: 0 AN: 27892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18630

East Asian (EAS) AF: 0.00 AC: 0 AN: 27125

South Asian (SAS) AF: 0.00 AC: 0 AN: 49769

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37629

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4088

European-Non Finnish (NFE) AF: 0.0000318 AC: 26 AN: 818866

Other (OTH) AF: 0.0000225 AC: 1 AN: 44351

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112378 Hom.: 0 Cov.: 23 AF XY: 0.0000290 AC XY: 1 AN XY: 34526

African (AFR) AF: 0.00 AC: 0 AN: 30912

American (AMR) AF: 0.00 AC: 0 AN: 10679

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3563

South Asian (SAS) AF: 0.00 AC: 0 AN: 2681

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53248

Other (OTH) AF: 0.00 AC: 0 AN: 1510

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.0000113

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	0.19
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0030
DANN	Benign	0.88
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L
PhyloP100		-3.0
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.037
Sift	Benign	0.38	T
Sift4G	Benign	0.52	T
Polyphen		0.0090	B
Vest4		0.054
MutPred		0.13		Gain of helix (P = 0.0854)
MVP		0.85
MPC		0.023
ClinPred		0.058	T
GERP RS		-8.4
PromoterAI		0.12	Neutral
Varity_R		0.059
gMVP		0.073
Mutation Taster		=100/0	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: rs1363515397; hg19: chrX-150884684;