Variant rs56201241 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_022661.4(SPANXC):c.89G>C(p.Ser30Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.013 ( 31 hom., 21 hem., cov: 0)

Exomes 𝑓: 0.0050 ( 473 hom. 510 hem. )

Failed GnomAD Quality Control

Consequence

SPANXC
NM_022661.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75

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:):

SPANXA2-OT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071487427).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (586/43641) while in subpopulation AFR AF= 0.0389 (554/14246). AF 95% confidence interval is 0.0362. There are 31 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPANXC	NM_022661.4 linkuse as main transcript	c.89G>C	p.Ser30Thr	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 linkuse as main transcript	c.89G>C	p.Ser30Thr	missense_variant	2/2	1	NM_022661.4	ENSP00000351884.2		Q9NY87
SPANXA2-OT1	ENST00000662492.1 linkuse as main transcript	n.102+53885C>G		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

583

AN:

43616

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

AN XY:

9104

show subpopulations

Gnomad AFR

AF:

0.0388

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

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:

0.000408

Gnomad OTH

AF:

0.0121

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00498

AC:

2271

AN:

456312

Hom.:

473

Cov.:

AF XY:

0.00495

AC XY:

510

AN XY:

103074

show subpopulations

Gnomad4 AFR exome

AF:

0.0840

Gnomad4 AMR exome

AF:

0.00982

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000470

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00115

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

AF:

0.0134

AC:

586

AN:

43641

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

AN XY:

9119

show subpopulations

Gnomad4 AFR

AF:

0.0389

Gnomad4 AMR

AF:

0.00450

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000408

Gnomad4 OTH

AF:

0.0120

Alfa

AF:

0.511

Hom.:

6056

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.15

DEOGEN2

Benign

0.0069

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0071

Sift4G

Benign

0.91

Vest4

0.10

gMVP

0.0024

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over