Variant 4-48341878-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020846.2(SLAIN2):c.139G>C(p.Gly47Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000353 in 1,517,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

SLAIN2
NM_020846.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.809

Variant links:

Genes affected

SLAIN2 (HGNC:29282): (SLAIN motif family member 2) Involved in cytoplasmic microtubule organization; microtubule nucleation; and positive regulation of microtubule polymerization. Located in centrosome and cytosol. Colocalizes with microtubule plus-end. [provided by Alliance of Genome Resources, Apr 2022]

SLAIN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0059365034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLAIN2	NM_020846.2 linkuse as main transcript	c.139G>C	p.Gly47Arg	missense_variant	1/8	ENST00000264313.11	NP_065897.1	Q9P270A0A024R9T6
SLAIN2	XM_005248121.4 linkuse as main transcript	c.139G>C	p.Gly47Arg	missense_variant	1/9		XP_005248178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLAIN2	ENST00000264313.11 linkuse as main transcript	c.139G>C	p.Gly47Arg	missense_variant	1/8	1	NM_020846.2	ENSP00000264313.5		Q9P270

Frequencies

GnomAD3 genomes

AF:

0.000611

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.000681

AC:

AN:

111566

Hom.:

AF XY:

0.000584

AC XY:

AN XY:

61594

show subpopulations

Gnomad AFR exome

AF:

0.000435

Gnomad AMR exome

AF:

0.00161

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000436

Gnomad OTH exome

AF:

0.00159

GnomAD4 exome

AF:

0.000325

AC:

443

AN:

1364808

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

211

AN XY:

672734

show subpopulations

Gnomad4 AFR exome

AF:

0.000253

Gnomad4 AMR exome

AF:

0.00167

Gnomad4 ASJ exome

AF:

0.00311

Gnomad4 EAS exome

AF:

0.0000318

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000227

Gnomad4 OTH exome

AF:

0.000993

GnomAD4 genome

AF:

0.000604

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000769

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000655

Hom.:

Bravo

AF:

0.000805

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000303

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

Feb 23, 2023

The c.139G>C (p.G47R) alteration is located in exon 1 (coding exon 1) of the SLAIN2 gene. This alteration results from a G to C substitution at nucleotide position 139, causing the glycine (G) at amino acid position 47 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

0.17

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.017

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.57

MetaRNN

Benign

0.0059

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.040

REVEL

Benign

0.065

Sift

Benign

0.48

Sift4G

Benign

0.57

Polyphen

0.0010

Vest4

0.13

MVP

0.043

MPC

0.25

ClinPred

0.025

GERP RS

3.4

Varity_R

0.034

gMVP

0.21

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