chr2-216420381-C-G

Position:

chr2-216420381-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014140.4(SMARCAL1):c.945C>G(p.Ser315Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,614,134 control chromosomes in the GnomAD database, including 884 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 189 hom., cov: 32)

Exomes 𝑓: 0.028 ( 695 hom. )

Consequence

SMARCAL1
NM_014140.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.682

Variant links:

Genes affected

SMARCAL1 (HGNC:11102): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein shows sequence similarity to the E. coli RNA polymerase-binding protein HepA. Mutations in this gene are a cause of Schimke immunoosseous dysplasia (SIOD), an autosomal recessive disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction, and T-cell immunodeficiency. [provided by RefSeq, Jul 2008]

SMARCAL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018854737).

BP6

Variant 2-216420381-C-G is Benign according to our data. Variant chr2-216420381-C-G is described in ClinVar as [Benign]. Clinvar id is 197799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-216420381-C-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCAL1	NM_014140.4 linkuse as main transcript	c.945C>G	p.Ser315Arg	missense_variant	5/18	ENST00000357276.9
SMARCAL1	NM_001127207.2 linkuse as main transcript	c.945C>G	p.Ser315Arg	missense_variant	5/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCAL1	ENST00000357276.9 linkuse as main transcript	c.945C>G	p.Ser315Arg	missense_variant	5/18	2	NM_014140.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0411

AC:

6250

AN:

152170

Hom.:

187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0807

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.0204

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00890

Gnomad FIN

AF:

0.0138

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0296

Gnomad OTH

AF:

0.0401

GnomAD3 exomes

AF:

0.0248

AC:

6240

AN:

251388

Hom.:

126

AF XY:

0.0238

AC XY:

3228

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0842

Gnomad AMR exome

AF:

0.0175

Gnomad ASJ exome

AF:

0.0240

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00911

Gnomad FIN exome

AF:

0.0162

Gnomad NFE exome

AF:

0.0281

Gnomad OTH exome

AF:

0.0333

GnomAD4 exome

AF:

0.0278

AC:

40712

AN:

1461846

Hom.:

695

Cov.:

AF XY:

0.0272

AC XY:

19809

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0864

Gnomad4 AMR exome

AF:

0.0211

Gnomad4 ASJ exome

AF:

0.0248

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00881

Gnomad4 FIN exome

AF:

0.0160

Gnomad4 NFE exome

AF:

0.0290

Gnomad4 OTH exome

AF:

0.0320

GnomAD4 genome

AF:

0.0411

AC:

6258

AN:

152288

Hom.:

189

Cov.:

AF XY:

0.0397

AC XY:

2954

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0808

Gnomad4 AMR

AF:

0.0342

Gnomad4 ASJ

AF:

0.0204

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00912

Gnomad4 FIN

AF:

0.0138

Gnomad4 NFE

AF:

0.0296

Gnomad4 OTH

AF:

0.0392

Alfa

AF:

0.0292

Hom.:

Bravo

AF:

0.0442

TwinsUK

AF:

0.0310

AC:

115

ALSPAC

AF:

0.0304

AC:

117

ESP6500AA

AF:

0.0801

AC:

353

ESP6500EA

AF:

0.0290

AC:

249

ExAC

AF:

0.0257

AC:

3118

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.0309

EpiControl

AF:

0.0304

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Schimke immuno-osseous dysplasia

Benign:4

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 27, 2015	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2019	- -

Focal segmental glomerulosclerosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Aug 08, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;T;T;T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.61

.;T;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

L;L;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.54

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.19

T;T;D;T;T

Sift4G

Benign

0.49

T;T;T;T;T

Polyphen

0.80

P;P;.;.;.

Vest4

0.075

MutPred

0.096

Loss of glycosylation at S315 (P = 0.0138);Loss of glycosylation at S315 (P = 0.0138);.;.;.;

MPC

0.25

ClinPred

0.0068

GERP RS

-0.19

Varity_R

0.034

gMVP

0.25

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