NM_033085.3:c.365C>T

Variant names:

• chrX-151721926-C-T
• rs144817068
• NM_033085.3:c.365C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_033085.3(FATE1):​c.365C>T​(p.Ala122Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000678 in 1,208,736 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 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 0.000036 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000071 (0 hom. 29 hem.)
• Consequence: FATE1 NM_033085.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.875
• Publications: 3 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14509237).
• BS2: High Hemizygotes in GnomAdExome4 at 29 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.365C>T	p.Ala122Val	missense	Exon 4 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.365C>T	p.Ala122Val	missense	Exon 4 of 5	ENSP00000359375.3	Q969F0
	FATE1	ENST00000940339.1		c.365C>T	p.Ala122Val	missense	Exon 5 of 6	ENSP00000610398.1
	FATE1	ENST00000940340.1		c.365C>T	p.Ala122Val	missense	Exon 5 of 6	ENSP00000610399.1

Frequencies

GnomAD3 genomes AF: 0.0000361 AC: 4 AN: 110773 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: 0.0000756

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000273 AC: 5 AN: 183282 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000489

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000710 AC: 78 AN: 1097963 Hom.: 0 Cov.: 30 AF XY: 0.0000798 AC XY: 29 AN XY: 363339

African (AFR) AF: 0.00 AC: 0 AN: 26400

American (AMR) AF: 0.00 AC: 0 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19378

East Asian (EAS) AF: 0.0000662 AC: 2 AN: 30205

South Asian (SAS) AF: 0.0000554 AC: 3 AN: 54133

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40509

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4137

European-Non Finnish (NFE) AF: 0.0000808 AC: 68 AN: 841911

Other (OTH) AF: 0.0000868 AC: 4 AN: 46088

GnomAD4 genome AF: 0.0000361 AC: 4 AN: 110773 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 32999

African (AFR) AF: 0.00 AC: 0 AN: 30376

American (AMR) AF: 0.00 AC: 0 AN: 10406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3517

South Asian (SAS) AF: 0.00 AC: 0 AN: 2528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000756 AC: 4 AN: 52912

Other (OTH) AF: 0.00 AC: 0 AN: 1493

Alfa AF: 0.0000725 Hom.: 3

Bravo AF: 0.0000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.12
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.88
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.074
Sift	Benign	0.069	T
Sift4G	Uncertain	0.047	D
Polyphen		0.95	P
Vest4		0.23
MVP		0.64
MPC		0.073
ClinPred		0.21	T
GERP RS		2.5
Varity_R		0.070
gMVP		0.11
Mutation Taster		=99/1	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: rs144817068; hg19: chrX-150890398; COSMIC: COSV64849161;