Variant X-143034239-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001009613.4(SPANXN4):c.293A>G(p.Gln98Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,163,612 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 7 hem. )

Consequence

SPANXN4
NM_001009613.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

Variant links:

Genes affected

SPANXN4 (HGNC:33177): (SPANX family member N4) This gene represents one of several duplicated family members that are located on the X chromosome. This gene family encodes proteins that play a role in spermiogenesis. These proteins represent a specific subgroup of cancer/testis-associated antigens, and they may be candidates for tumor vaccines. This family member belongs to a subgroup of related genes that are present in all primates and rats and mice, and thus, it represents one of the ancestral family members. [provided by RefSeq, Sep 2009]

SPANXN4 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=0.022989899).

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPANXN4	NM_001009613.4 linkuse as main transcript	c.293A>G	p.Gln98Arg	missense_variant	2/2	ENST00000446864.2
SPANXN4	XM_017029543.1 linkuse as main transcript	c.286+7A>G		splice_region_variant, intron_variant
SPANXN4	XM_017029544.1 linkuse as main transcript	c.283+7A>G		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPANXN4	ENST00000446864.2 linkuse as main transcript	c.293A>G	p.Gln98Arg	missense_variant	2/2	1	NM_001009613.4	P2
SPANXN4	ENST00000370504.3 linkuse as main transcript	c.283+7A>G		splice_region_variant, intron_variant		5		A2

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34500

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:

0.000373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000606

AC:

AN:

115464

Hom.:

AF XY:

0.000112

AC XY:

AN XY:

35804

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:

0.000576

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

1051204

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

339196

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:

0.000310

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000122

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000890

AC:

AN:

112408

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34562

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:

0.000374

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000382

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2023

The c.293A>G (p.Q98R) alteration is located in exon 2 (coding exon 2) of the SPANXN4 gene. This alteration results from a A to G substitution at nucleotide position 293, causing the glutamine (Q) at amino acid position 98 to be replaced by an arginine (R). 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

0.090

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-1.0

CADD

Benign

9.7

DANN

Benign

0.22

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.18

M_CAP

Benign

0.0012

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.3

REVEL

Benign

0.057

Sift

Uncertain

0.019

Sift4G

Uncertain

0.044

Polyphen

0.0030

Vest4

0.0090

MutPred

0.13

Gain of catalytic residue at Q98 (P = 0.06);

MVP

0.067

MPC

0.00084

ClinPred

0.024

GERP RS

1.4

Varity_R

0.11

gMVP

0.0028

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