Variant X-143034038-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001009613.4(SPANXN4):c.92T>C(p.Leu31Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000555 in 1,171,662 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L31M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000050 ( 0 hom. 15 hem. )

Consequence

SPANXN4
NM_001009613.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.843

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09370071).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPANXN4	NM_001009613.4 linkuse as main transcript	c.92T>C	p.Leu31Pro	missense_variant	2/2	ENST00000446864.2
SPANXN4	XM_017029543.1 linkuse as main transcript	c.92T>C	p.Leu31Pro	missense_variant	2/4
SPANXN4	XM_017029544.1 linkuse as main transcript	c.89T>C	p.Leu30Pro	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPANXN4	ENST00000446864.2 linkuse as main transcript	c.92T>C	p.Leu31Pro	missense_variant	2/2	1	NM_001009613.4	P2
SPANXN4	ENST00000370504.3 linkuse as main transcript	c.89T>C	p.Leu30Pro	missense_variant	2/3	5		A2

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

112144

Hom.:

Cov.:

AF XY:

0.0000874

AC XY:

AN XY:

34316

show subpopulations

Gnomad AFR

AF:

0.0000325

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000326

AC:

AN:

122660

Hom.:

AF XY:

0.0000259

AC XY:

AN XY:

38560

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:

0.0000799

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000500

AC:

AN:

1059518

Hom.:

Cov.:

AF XY:

0.0000435

AC XY:

AN XY:

344768

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000644

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000107

AC:

AN:

112144

Hom.:

Cov.:

AF XY:

0.0000874

AC XY:

AN XY:

34316

show subpopulations

Gnomad4 AFR

AF:

0.0000325

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:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000628

AC:

ExAC

AF:

0.0000365

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

Jan 24, 2024

The c.92T>C (p.L31P) alteration is located in exon 2 (coding exon 2) of the SPANXN4 gene. This alteration results from a T to C substitution at nucleotide position 92, causing the leucine (L) at amino acid position 31 to be replaced by a proline (P). 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

0.13

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0017

T;.

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.18

T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.094

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

2.8

N;N

REVEL

Benign

0.16

Sift

Benign

0.14

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.97

D;.

Vest4

0.27

MVP

0.12

MPC

0.00085

ClinPred

0.079

GERP RS

-1.6

Varity_R

0.27

gMVP

0.0022

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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