NM_001009613.4:c.293A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/20 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

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPANXN4	NM_001009613.4 link	c.293A>G	p.Gln98Arg	missense_variant	Exon 2 of 2	ENST00000446864.2	NP_001009613.1	Q5MJ08
SPANXN4	XM_017029543.1 link	c.286+7A>G		splice_region_variant, intron_variant	Intron 2 of 3		XP_016885032.1
SPANXN4	XM_017029544.1 link	c.283+7A>G		splice_region_variant, intron_variant	Intron 2 of 3		XP_016885033.1	X6R7N2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPANXN4	ENST00000446864.2 link	c.293A>G	p.Gln98Arg	missense_variant	Exon 2 of 2	1	NM_001009613.4	ENSP00000405210.1		Q5MJ08
SPANXN4	ENST00000370504.3 link	c.283+7A>G		splice_region_variant, intron_variant	Intron 2 of 2	5		ENSP00000359535.3		X6R7N2

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112356

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000606

AC:

AN:

115464

AF XY:

0.000112

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 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

African (AFR)

AF:

0.00

AC:

AN:

24765

American (AMR)

AF:

0.00

AC:

AN:

27401

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18305

East Asian (EAS)

AF:

0.00

AC:

AN:

27622

South Asian (SAS)

AF:

0.000310

AC:

AN:

48445

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4031

European-Non Finnish (NFE)

AF:

0.00000122

AC:

AN:

818362

Other (OTH)

AF:

0.00

AC:

AN:

44303

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000890

AC:

AN:

112408

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34562

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30966

American (AMR)

AF:

0.00

AC:

AN:

10647

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2655

East Asian (EAS)

AF:

0.00

AC:

AN:

3544

South Asian (SAS)

AF:

0.000374

AC:

AN:

2674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6207

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53290

Other (OTH)

AF:

0.00

AC:

AN:

1522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Oct 25, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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

PhyloP100

1.4

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

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over