Variant rs72630038 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001013627.3(NHSL2):c.586G>A(p.Glu196Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 1,165,875 control chromosomes in the GnomAD database, including 262 homozygotes. There are 1,940 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0054 ( 30 hom., 204 hem., cov: 25)

Exomes 𝑓: 0.0049 ( 232 hom. 1736 hem. )

Consequence

NHSL2
NM_001013627.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.45

Variant links:

Genes affected

NHSL2 (HGNC:33737): (NHS like 2) Predicted to enable calcium ion binding activity. Predicted to be involved in cell differentiation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NHSL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015164912).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHSL2	NM_001013627.3 linkuse as main transcript	c.586G>A	p.Glu196Lys	missense_variant	4/8	ENST00000633930.2	NP_001013649.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHSL2	ENST00000633930.2 linkuse as main transcript	c.586G>A	p.Glu196Lys	missense_variant	4/8	5	NM_001013627.3	ENSP00000488668	P3	Q5HYW2-1

Frequencies

GnomAD3 genomes

AF:

0.00545

AC:

616

AN:

112996

Hom.:

Cov.:

AF XY:

0.00583

AC XY:

205

AN XY:

35136

show subpopulations

Gnomad AFR

AF:

0.000770

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00296

Gnomad ASJ

AF:

0.00677

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000375

Gnomad OTH

AF:

0.00393

GnomAD3 exomes

AF:

0.0111

AC:

1245

AN:

112033

Hom.:

AF XY:

0.0105

AC XY:

420

AN XY:

39949

show subpopulations

Gnomad AFR exome

AF:

0.000316

Gnomad AMR exome

AF:

0.000258

Gnomad ASJ exome

AF:

0.00601

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.00324

Gnomad FIN exome

AF:

0.0000862

Gnomad NFE exome

AF:

0.000442

Gnomad OTH exome

AF:

0.00688

GnomAD4 exome

AF:

0.00490

AC:

5156

AN:

1052826

Hom.:

232

Cov.:

AF XY:

0.00505

AC XY:

1736

AN XY:

343674

show subpopulations

Gnomad4 AFR exome

AF:

0.000241

Gnomad4 AMR exome

AF:

0.000287

Gnomad4 ASJ exome

AF:

0.00693

Gnomad4 EAS exome

AF:

0.160

Gnomad4 SAS exome

AF:

0.00369

Gnomad4 FIN exome

AF:

0.0000798

Gnomad4 NFE exome

AF:

0.000249

Gnomad4 OTH exome

AF:

0.00654

GnomAD4 genome

AF:

0.00543

AC:

614

AN:

113049

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

204

AN XY:

35199

show subpopulations

Gnomad4 AFR

AF:

0.000768

Gnomad4 AMR

AF:

0.00296

Gnomad4 ASJ

AF:

0.00677

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000375

Gnomad4 OTH

AF:

0.00324

Alfa

AF:

0.00172

Hom.:

Bravo

AF:

0.00658

ExAC

AF:

0.00525

AC:

120

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Spinocerebellar ataxia, X-linked

Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

Vavilov Institute of General Genetics RAS, Laboratory of Evolutional Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.88

P;P;P;P

PrimateAI

Benign

0.43

Sift4G

Benign

0.10

T;.

Vest4

0.040

ClinPred

0.0072

GERP RS

3.4

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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