X-141241547-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.602

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 -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 GnomAd at 5 gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPANXC	ENST00000358993.3	c.264G>A	p.Met88Ile	missense_variant	2/2	1	NM_022661.4	P1
SPANXA2-OT1	ENST00000662492.1	n.102+53710C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000280 AC: 18 AN: 64340 Hom.: 0 Cov.: 9 AF XY: 0.000446 AC XY: 5 AN XY: 11212

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: 22 AN: 161982 Hom.: 0 AF XY: 0.0000371 AC XY: 2 AN XY: 53930

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.: 2 Cov.: 27 AF XY: 0.000191 AC XY: 58 AN XY: 303252

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: 18 AN: 64356 Hom.: 0 Cov.: 9 AF XY: 0.000445 AC XY: 5 AN XY: 11236

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.: 2

ExAC AF: 0.0000606 AC: 7

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.84
Cadd	Benign	8.5
Dann	Benign	0.69
DEOGEN2	Benign	0.0067	T
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.00084	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.067
Sift	Benign	0.060	T
Sift4G	Benign	0.79	T
Polyphen		0.70	P
Vest4		0.042
MutPred		0.61		Loss of loop (P = 0.1258);
MVP		0.14
MPC		2.7
ClinPred		0.066	T
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

Other links and lift over

dbSNP: rs199904329; hg19: chrX-140335680; COSMIC: COSV99082078;