rs3830139

Variant names:

• chr6-100448413-T-C
• rs3830139
• NM_005068.3:c.743+66A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-100448413-T-C
• chr6-100448413-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005068.3(SIM1):​c.743+66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000512 in 1,367,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: SIM1 NM_005068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• obesity due to SIM1 deficiency

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIM1	NM_005068.3	c.743+66A>G		intron_variant	Intron 7 of 11	ENST00000369208.8	NP_005059.2
SIM1	NM_001374769.1	c.743+66A>G		intron_variant	Intron 7 of 11		NP_001361698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIM1	ENST00000369208.8	c.743+66A>G		intron_variant	Intron 7 of 11	1	NM_005068.3	ENSP00000358210.4
SIM1	ENST00000262901.4	c.743+66A>G		intron_variant	Intron 6 of 10	1		ENSP00000262901.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000512 AC: 7 AN: 1367912 Hom.: 0 Cov.: 22 AF XY: 0.00000442 AC XY: 3 AN XY: 678126

African (AFR) AF: 0.00 AC: 0 AN: 31140

American (AMR) AF: 0.00 AC: 0 AN: 38566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24098

East Asian (EAS) AF: 0.00 AC: 0 AN: 37328

South Asian (SAS) AF: 0.00 AC: 0 AN: 79742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4616

European-Non Finnish (NFE) AF: 0.00000670 AC: 7 AN: 1044862

Other (OTH) AF: 0.00 AC: 0 AN: 56776

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.9
DANN	Benign	0.74
PhyloP100		0.34

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

Other links and lift over

dbSNP: rs3830139; hg19: chr6-100896289;