Variant 6-100448693-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005068.3(SIM1):c.544-15A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,602,516 control chromosomes in the GnomAD database, including 75,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7178 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68220 hom. )

Consequence

SIM1
NM_005068.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.284

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:

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 (BayesDel_noAF=-0.85).

BP6

Variant 6-100448693-T-G is Benign according to our data. Variant chr6-100448693-T-G is described in ClinVar as [Benign]. Clinvar id is 354686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIM1	NM_005068.3 linkuse as main transcript	c.544-15A>C		intron_variant		ENST00000369208.8	NP_005059.2	P81133
SIM1	NM_001374769.1 linkuse as main transcript	c.544-15A>C		intron_variant			NP_001361698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIM1	ENST00000369208.8 linkuse as main transcript	c.544-15A>C		intron_variant		1	NM_005068.3	ENSP00000358210.4		P81133
SIM1	ENST00000262901.4 linkuse as main transcript	c.544-15A>C		intron_variant		1		ENSP00000262901.4		P81133

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46019

AN:

151762

Hom.:

7170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.283

GnomAD3 exomes

AF:

0.315

AC:

76365

AN:

242440

Hom.:

12657

AF XY:

0.307

AC XY:

40369

AN XY:

131568

show subpopulations

Gnomad AFR exome

AF:

0.268

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.247

Gnomad EAS exome

AF:

0.437

Gnomad SAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.289

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.304

AC:

440343

AN:

1450636

Hom.:

68220

Cov.:

AF XY:

0.301

AC XY:

217102

AN XY:

721494

show subpopulations

Gnomad4 AFR exome

AF:

0.267

Gnomad4 AMR exome

AF:

0.429

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.451

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.300

Gnomad4 OTH exome

AF:

0.300

GnomAD4 genome

AF:

0.303

AC:

46054

AN:

151880

Hom.:

7178

Cov.:

AF XY:

0.308

AC XY:

22846

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.270

Gnomad4 AMR

AF:

0.375

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.444

Gnomad4 SAS

AF:

0.228

Gnomad4 FIN

AF:

0.342

Gnomad4 NFE

AF:

0.300

Gnomad4 OTH

AF:

0.280

Alfa

AF:

0.294

Hom.:

1991

Bravo

AF:

0.308

Asia WGS

AF:

0.306

AC:

1062

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Obesity due to SIM1 deficiency

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.5

DANN

Benign

0.37

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