X-141241722-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_022661.4(SPANXC):​c.89G>A​(p.Ser30Asn) 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: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom. 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09128913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPANXC	NM_022661.4	c.89G>A	p.Ser30Asn	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>A	p.Ser30Asn	missense_variant	Exon 2 of 2	1	NM_022661.4	ENSP00000351884.2
SPANXA2-OT1	ENST00000662492.1	n.102+53885C>T		intron_variant	Intron 2 of 5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 457046 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 103320

African (AFR) AF: 0.00 AC: 0 AN: 17346

American (AMR) AF: 0.00 AC: 0 AN: 19403

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 11154

South Asian (SAS) AF: 0.00 AC: 0 AN: 21280

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1295

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 338821

Other (OTH) AF: 0.00 AC: 0 AN: 20290

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.024
DEOGEN2	Benign	0.00066	T
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.091	T
PhyloP100		-1.7
Sift4G	Benign	0.74	T
Vest4		0.10
gMVP		0.0013

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;