Variant 21-36719859-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005069.6(SIM2):c.387T>C(p.His129=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,612,770 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 27 hom. )

Consequence

SIM2
NM_005069.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.50

Variant links:

Genes affected

SIM2 (HGNC:10883): (SIM bHLH transcription factor 2) This gene represents a homolog of the Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of neurogenesis. The encoded protein is ubiquitinated by RING-IBR-RING-type E3 ubiquitin ligases, including the parkin RBR E3 ubiquitin protein ligase. This gene maps within the so-called Down syndrome chromosomal region, and is thus thought to contribute to some specific Down syndrome phenotypes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

SIM2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 21-36719859-T-C is Benign according to our data. Variant chr21-36719859-T-C is described in ClinVar as [Benign]. Clinvar id is 779193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.5 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIM2	NM_005069.6 linkuse as main transcript	c.387T>C	p.His129=	synonymous_variant	4/11	ENST00000290399.11	NP_005060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIM2	ENST00000290399.11 linkuse as main transcript	c.387T>C	p.His129=	synonymous_variant	4/11	1	NM_005069.6	ENSP00000290399	P1	Q14190-1
SIM2	ENST00000431229.1 linkuse as main transcript	c.201T>C	p.His67=	synonymous_variant	3/10	1		ENSP00000392003
SIM2	ENST00000483178.2 linkuse as main transcript	c.96T>C	p.His32=	synonymous_variant	2/2	3		ENSP00000476273
SIM2	ENST00000481185.1 linkuse as main transcript	n.1000T>C		non_coding_transcript_exon_variant	4/10	2

Frequencies

GnomAD3 genomes

AF:

0.00302

AC:

458

AN:

151440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000535

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00835

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000774

Gnomad SAS

AF:

0.00792

Gnomad FIN

AF:

0.00220

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00350

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00513

AC:

1291

AN:

251442

Hom.:

AF XY:

0.00529

AC XY:

719

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.0120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.00911

Gnomad FIN exome

AF:

0.00329

Gnomad NFE exome

AF:

0.00424

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00400

AC:

5840

AN:

1461212

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

3079

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.0120

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.00953

Gnomad4 FIN exome

AF:

0.00418

Gnomad4 NFE exome

AF:

0.00359

Gnomad4 OTH exome

AF:

0.00363

GnomAD4 genome

AF:

0.00302

AC:

458

AN:

151558

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

242

AN XY:

74014

show subpopulations

Gnomad4 AFR

AF:

0.000534

Gnomad4 AMR

AF:

0.00834

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000775

Gnomad4 SAS

AF:

0.00793

Gnomad4 FIN

AF:

0.00220

Gnomad4 NFE

AF:

0.00350

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00286

Hom.:

Bravo

AF:

0.00310

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00403

EpiControl

AF:

0.00403

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.8

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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