rs56201241

Variant names:

• chrX-141241722-C-G
• rs56201241
• NM_022661.4:c.89G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-141241722-C-G
• chrX-141241722-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong 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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0071487427).
• BS2: High Homozygotes in GnomAd4 at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPANXC	NM_022661.4	c.89G>C	p.Ser30Thr	missense_variant	Exon 2 of 2	ENST00000358993.3	NP_073152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPANXC	ENST00000358993.3	c.89G>C	p.Ser30Thr	missense_variant	Exon 2 of 2	1	NM_022661.4	ENSP00000351884.2
SPANXA2-OT1	ENST00000662492.1	n.102+53885C>G		intron_variant	Intron 2 of 5

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 583 AN: 43616 Hom.: 31 Cov.: 0

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0840 AC: 1411 AN: 16803

American (AMR) AF: 0.00982 AC: 190 AN: 19356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8611

East Asian (EAS) AF: 0.00 AC: 0 AN: 11152

South Asian (SAS) AF: 0.000470 AC: 10 AN: 21278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18846

Middle Eastern (MID) AF: 0.0217 AC: 28 AN: 1289

European-Non Finnish (NFE) AF: 0.00115 AC: 388 AN: 338735

Other (OTH) AF: 0.0121 AC: 244 AN: 20242

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0134 AC: 586 AN: 43641 Hom.: 31 Cov.: 0 AF XY: 0.00230 AC XY: 21 AN XY: 9119

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0389 AC: 554 AN: 14246

American (AMR) AF: 0.00450 AC: 18 AN: 3996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1119

East Asian (EAS) AF: 0.00 AC: 0 AN: 717

South Asian (SAS) AF: 0.00 AC: 0 AN: 795

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 61

European-Non Finnish (NFE) AF: 0.000408 AC: 8 AN: 19594

Other (OTH) AF: 0.0120 AC: 6 AN: 498

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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
PhyloP100		-1.7
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

Other links and lift over

dbSNP: rs56201241; hg19: chrX-140335855;