rs1029968837

Variant names:

• chr6-100390233-G-A
• rs1029968837
• NM_005068.3:c.*128C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-100390233-G-A
• chr6-100390233-G-C
• chr6-100390233-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_005068.3(SIM1):​c.*128C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000898 in 1,001,990 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: SIM1 NM_005068.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• 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: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.00000941 (8/849848) while in subpopulation AFR AF = 0.0001 (2/19974). AF 95% confidence interval is 0.0000176. There are 0 homozygotes in GnomAdExome4. There are 5 alleles in the male GnomAdExome4 subpopulation. Median coverage is 11. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005068.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIM1	NM_005068.3	MANE Select	c.*128C>T		3_prime_UTR	Exon 12 of 12	NP_005059.2
	SIM1	NM_001374769.1		c.*128C>T		3_prime_UTR	Exon 12 of 12	NP_001361698.1	P81133

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIM1	ENST00000369208.8	TSL:1 MANE Select	c.*128C>T		3_prime_UTR	Exon 12 of 12	ENSP00000358210.4	P81133
	SIM1	ENST00000262901.4	TSL:1	c.*128C>T		3_prime_UTR	Exon 11 of 11	ENSP00000262901.4	P81133
	SIM1	ENST00000900753.1		c.*128C>T		3_prime_UTR	Exon 12 of 12	ENSP00000570812.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000941 AC: 8 AN: 849848 Hom.: 0 Cov.: 11 AF XY: 0.0000116 AC XY: 5 AN XY: 432220

African (AFR) AF: 0.000100 AC: 2 AN: 19974

American (AMR) AF: 0.00 AC: 0 AN: 25552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16712

East Asian (EAS) AF: 0.00 AC: 0 AN: 35612

South Asian (SAS) AF: 0.0000357 AC: 2 AN: 55990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3144

European-Non Finnish (NFE) AF: 0.00000647 AC: 4 AN: 618064

Other (OTH) AF: 0.00 AC: 0 AN: 39276

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74316

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.2
DANN	Benign	0.79
PhyloP100		0.21

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: rs1029968837; hg19: chr6-100838109; COSMIC: COSV53490632; COSMIC: COSV53490632;