Genetic Variant SPANXN3:p.Glu11Lys (chrX-143517361-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001009609.4(SPANXN3):c.31G>A(p.Glu11Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,209,662 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 90 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: 𝑓 0.00016 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.00027 ( 0 hom. 88 hem. )

Consequence

SPANXN3
NM_001009609.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0290

Variant links:

Genes affected

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

SPANXN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05371809).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPANXN3	NM_001009609.4 link	c.31G>A	p.Glu11Lys	missense_variant	Exon 1 of 2	ENST00000370503.2	NP_001009609.2	Q5MJ09

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPANXN3	ENST00000370503.2 link	c.31G>A	p.Glu11Lys	missense_variant	Exon 1 of 2	1	NM_001009609.4	ENSP00000359534.2		Q5MJ09

Frequencies

GnomAD3 genomes

AF:

0.000161

AC:

AN:

111678

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

33842

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000339

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000818

AC:

AN:

183266

Hom.:

AF XY:

0.0000591

AC XY:

AN XY:

67704

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000270

AC:

296

AN:

1097984

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

363360

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000343

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.000161

AC:

AN:

111678

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

33842

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000339

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000831

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.31G>A (p.E11K) alteration is located in exon 1 (coding exon 1) of the SPANXN3 gene. This alteration results from a G to A substitution at nucleotide position 31, causing the glutamic acid (E) at amino acid position 11 to be replaced by a lysine (K). 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

0.084

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.34

DANN

Benign

0.63

FATHMM_MKL

Benign

0.0017

M_CAP

Benign

0.0016

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.91

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.64

REVEL

Benign

0.012

Sift

Benign

0.61

Sift4G

Benign

0.56

Vest4

0.080

MVP

0.068

MPC

0.050

ClinPred

0.016

GERP RS

-1.9

gMVP

0.0077

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