X-151721485-C-T

Variant names:

• chrX-151721485-C-T
• rs748489127
• NM_033085.3:c.325C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_033085.3(FATE1):​c.325C>T​(p.Arg109Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000411 in 1,095,870 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R109H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000041 (0 hom. 14 hem.)
• Consequence: FATE1 NM_033085.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.246
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 14 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.325C>T	p.Arg109Cys	missense	Exon 3 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.325C>T	p.Arg109Cys	missense	Exon 3 of 5	ENSP00000359375.3	Q969F0
	FATE1	ENST00000940339.1		c.325C>T	p.Arg109Cys	missense	Exon 4 of 6	ENSP00000610398.1
	FATE1	ENST00000940340.1		c.325C>T	p.Arg109Cys	missense	Exon 4 of 6	ENSP00000610399.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000164 AC: 3 AN: 183280 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000144

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000411 AC: 45 AN: 1095870 Hom.: 0 Cov.: 30 AF XY: 0.0000388 AC XY: 14 AN XY: 361278

African (AFR) AF: 0.00 AC: 0 AN: 26352

American (AMR) AF: 0.0000284 AC: 1 AN: 35203

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19370

East Asian (EAS) AF: 0.0000662 AC: 2 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54067

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4075

European-Non Finnish (NFE) AF: 0.0000500 AC: 42 AN: 840048

Other (OTH) AF: 0.00 AC: 0 AN: 46018

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

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	-0.42	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0070	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.25
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.13
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.52		Loss of disorder (P = 0.0979)
MVP		0.73
MPC		0.18
ClinPred		0.52	D
GERP RS		-1.2
Varity_R		0.14
gMVP		0.15
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs748489127; hg19: chrX-150889957; COSMIC: COSV64848901;