6-100388146-T-C

Position:

• chr6-100388146-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005068.3(SIM1):​c.*2215A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,022 control chromosomes in the GnomAD database, including 4,227 homozygotes. 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 0.21 (4227 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SIM1 NM_005068.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIM1	NM_005068.3	c.*2215A>G		3_prime_UTR_variant	12/12	ENST00000369208.8	NP_005059.2
SIM1	NM_001374769.1	c.*2215A>G		3_prime_UTR_variant	12/12		NP_001361698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIM1	ENST00000369208.8	c.*2215A>G		3_prime_UTR_variant	12/12	1	NM_005068.3	ENSP00000358210	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31341 AN: 151906 Hom.: 4221 Cov.: 33

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.206 AC: 31359 AN: 152022 Hom.: 4227 Cov.: 33 AF XY: 0.214 AC XY: 15933 AN XY: 74296

Gnomad4 AFR AF: 0.0558

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.191

Alfa AF: 0.214 Hom.: 481

Bravo AF: 0.201

Asia WGS AF: 0.359 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.50

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: rs9386126; hg19: chr6-100836022;