6-100388760-A-T

Position:

• chr6-100388760-A-T

Variant summary

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

The ENST00000369208.8(SIM1):​c.*1601T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,124 control chromosomes in the GnomAD database, including 4,294 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 (4294 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SIM1 ENST00000369208.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIM1	NM_005068.3	c.*1601T>A		3_prime_UTR_variant	12/12	ENST00000369208.8	NP_005059.2
SIM1	NM_001374769.1	c.*1601T>A		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.*1601T>A		3_prime_UTR_variant	12/12	1	NM_005068.3	ENSP00000358210	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31465 AN: 152006 Hom.: 4287 Cov.: 32

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.320

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: 0.207 AC: 31483 AN: 152124 Hom.: 4294 Cov.: 32 AF XY: 0.215 AC XY: 16005 AN XY: 74346

Gnomad4 AFR AF: 0.0555

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.191

Alfa AF: 0.217 Hom.: 470

Bravo AF: 0.201

Asia WGS AF: 0.360 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.7
DANN	Benign	0.77

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: rs17060480; hg19: chr6-100836636;