Variant 6-100389424-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005068.3(SIM1):c.*937C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0069 in 392,600 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 10 hom. )

Consequence

SIM1
NM_005068.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.554

Variant links:

Genes affected

SIM1 (HGNC:10882): (SIM bHLH transcription factor 1) SIM1 and SIM2 genes are Drosophila single-minded (sim) gene homologs. SIM1 transcript was detected only in fetal kidney out of various adult and fetal tissues tested. Since the sim gene plays an important role in Drosophila development and has peak levels of expression during the period of neurogenesis,it was proposed that the human SIM gene is a candidate for involvement in certain dysmorphic features (particularly the facial and skull characteristics), abnormalities of brain development, and/or cognitive disability of Down syndrome. [provided by RefSeq, Jul 2008]

SIM1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-100389424-G-T is Benign according to our data. Variant chr6-100389424-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 905432.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 981 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIM1	NM_005068.3 linkuse as main transcript	c.*937C>A		3_prime_UTR_variant	12/12	ENST00000369208.8
SIM1	NM_001374769.1 linkuse as main transcript	c.*937C>A		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIM1	ENST00000369208.8 linkuse as main transcript	c.*937C>A		3_prime_UTR_variant	12/12	1	NM_005068.3	P1
SIM1	ENST00000262901.4 linkuse as main transcript	c.*937C>A		3_prime_UTR_variant	11/11	1		P1

Frequencies

GnomAD3 genomes

AF:

0.00646

AC:

981

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.0372

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00727

Gnomad OTH

AF:

0.00335

GnomAD4 exome

AF:

0.00718

AC:

1726

AN:

240542

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

861

AN XY:

122016

show subpopulations

Gnomad4 AFR exome

AF:

0.000844

Gnomad4 AMR exome

AF:

0.000819

Gnomad4 ASJ exome

AF:

0.000110

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000928

Gnomad4 FIN exome

AF:

0.0272

Gnomad4 NFE exome

AF:

0.00706

Gnomad4 OTH exome

AF:

0.00417

GnomAD4 genome

AF:

0.00645

AC:

981

AN:

152058

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

552

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.0372

Gnomad4 NFE

AF:

0.00727

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00485

Hom.:

Bravo

AF:

0.00382

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Obesity due to SIM1 deficiency

Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.28

DANN

Benign

0.35

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