6-100388356-G-GA

Position:

• chr6-100388356-G-GA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005068.3(SIM1):​c.*2004_*2005insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 151,512 control chromosomes in the GnomAD database, including 1,047 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1047 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIM1 NM_005068.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIM1	NM_005068.3	c.*2004_*2005insT		3_prime_UTR_variant	12/12	ENST00000369208.8
SIM1	NM_001374769.1	c.*2004_*2005insT		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIM1	ENST00000369208.8	c.*2004_*2005insT		3_prime_UTR_variant	12/12	1	NM_005068.3	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17681 AN: 151394 Hom.: 1035 Cov.: 30

Gnomad AFR AF: 0.0947

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.0881

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.125

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.117 AC: 17700 AN: 151512 Hom.: 1047 Cov.: 30 AF XY: 0.114 AC XY: 8460 AN XY: 74030

Gnomad4 AFR AF: 0.0946

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.0711

Gnomad4 FIN AF: 0.0881

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.135

Bravo AF: 0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs35180395; hg19: chr6-100836232;