X-143508901-C-A

Variant names:

• chrX-143508901-C-A
• rs782625849
• NM_001009609.4:c.340G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001009609.4(SPANXN3):​c.340G>T​(p.Asp114Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,098,036 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D114N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: SPANXN3 NM_001009609.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 0 publications found

Genes affected

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

ENSG00000227303 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18442273).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009609.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPANXN3	NM_001009609.4	MANE Select	c.340G>T	p.Asp114Tyr	missense	Exon 2 of 2	NP_001009609.2	Q5MJ09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPANXN3	ENST00000370503.2	TSL:1 MANE Select	c.340G>T	p.Asp114Tyr	missense	Exon 2 of 2	ENSP00000359534.2	Q5MJ09
	ENSG00000227303	ENST00000431432.1	TSL:3	n.269-708C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098036 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363396

African (AFR) AF: 0.00 AC: 0 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.0000662 AC: 2 AN: 30202

South Asian (SAS) AF: 0.00 AC: 0 AN: 54143

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841943

Other (OTH) AF: 0.00 AC: 0 AN: 46091

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.014	N
M_CAP	Benign	0.00097	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.073
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.030
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Vest4		0.24
MutPred		0.20		Gain of phosphorylation at D114 (P = 0.0033)
MVP		0.043
MPC		0.26
ClinPred		0.91	D
GERP RS		0.42
gMVP		0.016
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs782625849; hg19: chrX-142596730; COSMIC: COSV65140126;