rs9386144

chr6-100425381-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.999-4423A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,162 control chromosomes in the GnomAD database, including 2,932 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 0.18 (2932 hom., cov: 32)
• Consequence: SIM1 NM_005068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIM1	NM_005068.3	c.999-4423A>G		intron_variant		ENST00000369208.8
SIM1-AS1	XR_942815.4	n.891-1737T>C		intron_variant, non_coding_transcript_variant
SIM1	NM_001374769.1	c.999-4423A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIM1	ENST00000369208.8	c.999-4423A>G		intron_variant		1	NM_005068.3	P1
SIM1	ENST00000262901.4	c.999-4423A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26602 AN: 152044 Hom.: 2924 Cov.: 32

Gnomad AFR AF: 0.0459

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.173

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 26633 AN: 152162 Hom.: 2932 Cov.: 32 AF XY: 0.180 AC XY: 13402 AN XY: 74390

Gnomad4 AFR AF: 0.0462

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.173

Alfa AF: 0.192 Hom.: 552

Bravo AF: 0.168

Asia WGS AF: 0.273 AC: 947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	4.2
Dann	Benign	0.75

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: rs9386144; hg19: chr6-100873257;