X-143508907-C-T

Variant names:

• chrX-143508907-C-T
• rs1556411229
• NM_001009609.4:c.334G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001009609.4(SPANXN3):​c.334G>A​(p.Asp112Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 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: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: SPANXN3 NM_001009609.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0350

Genes affected

SPANXN3 (HGNC:33176): (SPANX family member N3)

ENSG00000227303 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10369244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPANXN3	NM_001009609.4	c.334G>A	p.Asp112Asn	missense_variant	Exon 2 of 2	ENST00000370503.2	NP_001009609.2
SPANXN3	XM_017029264.2	c.331G>A	p.Asp111Asn	missense_variant	Exon 2 of 2		XP_016884753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPANXN3	ENST00000370503.2	c.334G>A	p.Asp112Asn	missense_variant	Exon 2 of 2	1	NM_001009609.4	ENSP00000359534.2
ENSG00000227303	ENST00000431432.1	n.269-702C>T		intron_variant	Intron 3 of 5	3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000546 AC: 1 AN: 183254 Hom.: 0 AF XY: 0.0000148 AC XY: 1 AN XY: 67784

Gnomad AFR exome AF: 0.0000760

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000182 AC: 2 AN: 1098062 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 2 AN XY: 363422

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.334G>A (p.D112N) alteration is located in exon 2 (coding exon 2) of the SPANXN3 gene. This alteration results from a G to A substitution at nucleotide position 334, causing the aspartic acid (D) at amino acid position 112 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	12
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.0077	N
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.025
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0090	D
Vest4		0.085
MutPred		0.39		Gain of methylation at K113 (P = 0.1743);
MVP		0.068
MPC		0.27
ClinPred		0.19	T
GERP RS		-0.86
gMVP		0.0035

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: rs1556411229; hg19: chrX-142596736;