Variant X-141241547-C-T 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.264G>A(p.Met88Ile) 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 0.00028 ( 0 hom., 5 hem., cov: 9)

Exomes 𝑓: 0.00025 ( 2 hom. 58 hem. )

Failed GnomAD Quality Control

Consequence

SPANXC
NM_022661.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.602

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=0.02366817).

BP6

Variant X-141241547-C-T is Benign according to our data. Variant chrX-141241547-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661546.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPANXC	NM_022661.4 link	c.264G>A	p.Met88Ile	missense_variant	2/2	ENST00000358993.3	NP_073152.2	Q9NY87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPANXC	ENST00000358993.3 link	c.264G>A	p.Met88Ile	missense_variant	2/2	1	NM_022661.4	ENSP00000351884.2		Q9NY87
SPANXA2-OT1	ENST00000662492.1 link	n.102+53710C>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000280

AC:

AN:

64340

Hom.:

Cov.:

AF XY:

0.000446

AC XY:

AN XY:

11212

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000728

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00463

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000101

Gnomad OTH

AF:

0.00132

GnomAD3 exomes

AF:

0.000136

AC:

AN:

161982

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

53930

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000827

Gnomad SAS exome

AF:

0.000446

Gnomad FIN exome

AF:

0.0000666

Gnomad NFE exome

AF:

0.0000951

Gnomad OTH exome

AF:

0.000249

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000246

AC:

246

AN:

1001296

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

AN XY:

303252

show subpopulations

Gnomad4 AFR exome

AF:

0.000608

Gnomad4 AMR exome

AF:

0.0000590

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000723

Gnomad4 SAS exome

AF:

0.00196

Gnomad4 FIN exome

AF:

0.0000256

Gnomad4 NFE exome

AF:

0.000149

Gnomad4 OTH exome

AF:

0.000259

GnomAD4 genome

AF:

0.000280

AC:

AN:

64356

Hom.:

Cov.:

AF XY:

0.000445

AC XY:

AN XY:

11236

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000728

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00466

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000101

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.000336

Hom.:

ExAC

AF:

0.0000606

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

Mar 01, 2023

SPANXC: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.5

DANN

Benign

0.69

DEOGEN2

Benign

0.0067

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.45

M_CAP

Benign

0.00084

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.96

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.44

REVEL

Benign

0.067

Sift

Benign

0.060

Sift4G

Benign

0.79

Polyphen

0.70

Vest4

0.042

MutPred

0.61

Loss of loop (P = 0.1258);

MVP

0.14

MPC

2.7

ClinPred

0.066

Varity_R

0.43

gMVP

0.0024

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