Genetic Variant SPANXN3:p.Gly107Glu (chrX-143508921-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001009609.4(SPANXN3):c.320G>A(p.Gly107Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000546 in 1,097,978 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000055 ( 0 hom. 1 hem. )

Consequence

SPANXN3
NM_001009609.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.382

Variant links:

Genes affected

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

SPANXN3 links:

ENSG00000227303 (HGNC:):

ENSG00000227303 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07000047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPANXN3	NM_001009609.4 link	c.320G>A	p.Gly107Glu	missense_variant	Exon 2 of 2	ENST00000370503.2	NP_001009609.2	Q5MJ09
SPANXN3	XM_017029264.2 link	c.317G>A	p.Gly106Glu	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 link	c.320G>A	p.Gly107Glu	missense_variant	Exon 2 of 2	1	NM_001009609.4	ENSP00000359534.2		Q5MJ09
ENSG00000227303	ENST00000431432.1 link	n.269-688C>T		intron_variant	Intron 3 of 5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

183289

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67803

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000157

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000546

AC:

AN:

1097978

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363340

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000739

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.320G>A (p.G107E) 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 320, causing the glycine (G) at amino acid position 107 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.25

DANN

Benign

0.49

FATHMM_MKL

Benign

0.0050

M_CAP

Benign

0.00053

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.3

REVEL

Benign

0.017

Sift

Benign

0.16

Sift4G

Benign

0.12

Vest4

0.049

MutPred

0.29

Gain of solvent accessibility (P = 0.024);

MVP

0.043

MPC

0.045

ClinPred

0.021

GERP RS

-2.1

gMVP

0.0011

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over