X-151722709-G-C

Variant names:

• chrX-151722709-G-C
• rs774947821
• NM_033085.3:c.502G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_033085.3(FATE1):​c.502G>C​(p.Val168Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: FATE1 NM_033085.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.02
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028041512).
• BP6: Variant X-151722709-G-C is Benign according to our data. Variant chrX-151722709-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2492873.Status of the report is criteria_provided_single_submitter, 1 stars.

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.502G>C	p.Val168Leu	missense	Exon 5 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.502G>C	p.Val168Leu	missense	Exon 5 of 5	ENSP00000359375.3	Q969F0
	FATE1	ENST00000940339.1		c.502G>C	p.Val168Leu	missense	Exon 6 of 6	ENSP00000610398.1
	FATE1	ENST00000940340.1		c.502G>C	p.Val168Leu	missense	Exon 6 of 6	ENSP00000610399.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.12
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.0010
DANN	Benign	0.51
DEOGEN2	Benign	0.013	T
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-3.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.012
Sift	Benign	0.55	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.038
MutPred		0.37		Loss of MoRF binding (P = 0.0929)
MVP		0.40
MPC		0.021
ClinPred		0.028	T
GERP RS		-8.8
Varity_R		0.060
gMVP		0.11
Mutation Taster		=97/3	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: rs774947821; hg19: chrX-150891181;