Variant X-141241617-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022661.4(SPANXC):c.194A>G(p.Glu65Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 5 hom., 25 hem., cov: 9)

Exomes 𝑓: 0.00024 ( 1 hom. 42 hem. )

Failed GnomAD Quality Control

Consequence

SPANXC
NM_022661.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.70

Variant links:

Genes affected

SPANXC (HGNC:14331): (SPANX family member C) Temporally regulated transcription and translation of several testis-specific genes is required to initiate the series of molecular and morphological changes in the male germ cell lineage necessary for the formation of mature spermatozoa. This gene is a member of the SPANX family, which is located in a gene cluster on chromosome X. The SPANX genes encode differentially expressed testis-specific proteins that localize to various subcellular compartments. This particular gene encodes a protein that localizes to the nucleus and is expressed in highly metastatic cell lines, making the protein a potential diagnostic and prognostic marker. The protein belongs to a family of cancer/testis antigens and represents a potential target for cancer immunotherapy. [provided by RefSeq, Jul 2008]

SPANXC links:

SPANXA2-OT1 (HGNC:31683): (SPANXA2 overlapping transcript 1)

SPANXA2-OT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0109600425).

BP6

Variant X-141241617-T-C is Benign according to our data. Variant chrX-141241617-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2661547.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPANXC	NM_022661.4 linkuse as main transcript	c.194A>G	p.Glu65Gly	missense_variant	2/2	ENST00000358993.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPANXC	ENST00000358993.3 linkuse as main transcript	c.194A>G	p.Glu65Gly	missense_variant	2/2	1	NM_022661.4	P1
SPANXA2-OT1	ENST00000662492.1 linkuse as main transcript	n.102+53780T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00238

AC:

148

AN:

62099

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

AN XY:

11463

show subpopulations

Gnomad AFR

AF:

0.00703

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

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:

0.0000350

Gnomad OTH

AF:

0.00135

GnomAD3 exomes

AF:

0.000124

AC:

AN:

177640

Hom.:

AF XY:

0.0000477

AC XY:

AN XY:

62956

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.000112

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000379

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000242

AC:

259

AN:

1070805

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

343339

show subpopulations

Gnomad4 AFR exome

AF:

0.00547

Gnomad4 AMR exome

AF:

0.000461

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000996

Gnomad4 OTH exome

AF:

0.000448

GnomAD4 genome

AF:

0.00238

AC:

148

AN:

62112

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

AN XY:

11486

show subpopulations

Gnomad4 AFR

AF:

0.00702

Gnomad4 AMR

AF:

0.00110

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000350

Gnomad4 OTH

AF:

0.00134

Alfa

AF:

0.00160

Hom.:

ExAC

AF:

0.000227

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

SPANXA2-OT1: BS2; SPANXC: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.4

DANN

Benign

0.53

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.00036

LIST_S2

Benign

0.32

M_CAP

Benign

0.0015

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.5

REVEL

Benign

0.023

Sift

Benign

0.25

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.17

MVP

0.10

MPC

1.9

ClinPred

0.20

Varity_R

0.13

gMVP

0.0039

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over