rs56201241

chrX-141241722-C-GchrX-141241722-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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]

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

ACMG classification

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 GnomAd at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPANXC	NM_022661.4	c.89G>C	p.Ser30Thr	missense_variant	2/2	ENST00000358993.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPANXC	ENST00000358993.3	c.89G>C	p.Ser30Thr	missense_variant	2/2	1	NM_022661.4	P1
SPANXA2-OT1	ENST00000662492.1	n.102+53885C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 583 AN: 43616 Hom.: 31 Cov.: 0 AF XY: 0.00220 AC XY: 20 AN XY: 9104

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.: 4 AF XY: 0.00495 AC XY: 510 AN XY: 103074

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.: 31 Cov.: 0 AF XY: 0.00230 AC XY: 21 AN XY: 9119

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	T
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0071	T
Sift4G	Benign	0.91	T
Vest4		0.10
gMVP		0.0024

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56201241; hg19: chrX-140335855;