rs9386144

Variant names:

• chr6-100425381-T-C
• rs9386144
• NM_005068.3:c.999-4423A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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-AS1 (HGNC:40530): (SIM1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SIM1	NM_005068.3	c.999-4423A>G		intron_variant	Intron 9 of 11	ENST00000369208.8	NP_005059.2
SIM1	NM_001374769.1	c.999-4423A>G		intron_variant	Intron 9 of 11		NP_001361698.1
SIM1-AS1	NR_187148.1	n.891-1737T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIM1	ENST00000369208.8	c.999-4423A>G		intron_variant	Intron 9 of 11	1	NM_005068.3	ENSP00000358210.4
SIM1	ENST00000262901.4	c.999-4423A>G		intron_variant	Intron 8 of 10	1		ENSP00000262901.4

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

African (AFR) AF: 0.0462 AC: 1921 AN: 41542

American (AMR) AF: 0.229 AC: 3503 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 546 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2241 AN: 5174

South Asian (SAS) AF: 0.225 AC: 1086 AN: 4830

European-Finnish (FIN) AF: 0.254 AC: 2690 AN: 10572

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14047 AN: 67976

Other (OTH) AF: 0.173 AC: 364 AN: 2110

Alfa AF: 0.147 Hom.: 613

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
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs9386144; hg19: chr6-100873257;