Genetic Variant FATE1:p.Arg159Ser (chrX-151722682-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033085.3(FATE1):c.475C>A(p.Arg159Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,097,798 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 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. R159H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.0000064 ( 0 hom. 1 hem. )

Consequence

FATE1
NM_033085.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.759

Publications

0 publications found

Variant links:

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]

FATE1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14200014).

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.475C>A	p.Arg159Ser	missense	Exon 5 of 5	NP_149076.1	Q969F0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FATE1	ENST00000370350.7	TSL:1 MANE Select	c.475C>A	p.Arg159Ser	missense	Exon 5 of 5	ENSP00000359375.3	Q969F0
FATE1	ENST00000940339.1		c.475C>A	p.Arg159Ser	missense	Exon 6 of 6	ENSP00000610398.1
FATE1	ENST00000940340.1		c.475C>A	p.Arg159Ser	missense	Exon 6 of 6	ENSP00000610399.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000165

AC:

AN:

181784

AF XY:

0.00

show subpopulations

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:

0.0000372

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000638

AC:

AN:

1097798

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26388

American (AMR)

AF:

0.00

AC:

AN:

35172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19370

East Asian (EAS)

AF:

0.00

AC:

AN:

30193

South Asian (SAS)

AF:

0.00

AC:

AN:

54099

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40457

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4125

European-Non Finnish (NFE)

AF:

0.00000831

AC:

AN:

841925

Other (OTH)

AF:

0.00

AC:

AN:

46069

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.048

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

-0.76

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.9

REVEL

Benign

0.038

Sift

Benign

0.054

Sift4G

Benign

0.082

Polyphen

0.92

Vest4

0.068

MutPred

0.25

Loss of MoRF binding (P = 0.0367)

MVP

0.82

MPC

0.15

ClinPred

0.36

GERP RS

-0.76

Varity_R

0.37

gMVP

0.43

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over