6-100417062-T-G

Variant names:

• chr6-100417062-T-G
• rs9390366
• NM_005068.3:c.1167+3728A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005068.3(SIM1):​c.1167+3728A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,946 control chromosomes in the GnomAD database, including 4,423 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 0.22 (4423 hom., cov: 31)
• Consequence: SIM1 NM_005068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005068.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIM1	NM_005068.3	MANE Select	c.1167+3728A>C		intron	N/A	NP_005059.2
	SIM1	NM_001374769.1		c.1167+3728A>C		intron	N/A	NP_001361698.1	P81133
	SIM1-AS1	NR_187148.1		n.891-10056T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIM1	ENST00000369208.8	TSL:1 MANE Select	c.1167+3728A>C		intron	N/A	ENSP00000358210.4	P81133
	SIM1	ENST00000262901.4	TSL:1	c.1167+3728A>C		intron	N/A	ENSP00000262901.4	P81133
	SIM1	ENST00000900753.1		c.1167+3728A>C		intron	N/A	ENSP00000570812.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33053 AN: 151828 Hom.: 4412 Cov.: 31

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.218 AC: 33091 AN: 151946 Hom.: 4423 Cov.: 31 AF XY: 0.226 AC XY: 16741 AN XY: 74224

African (AFR) AF: 0.0934 AC: 3874 AN: 41482

American (AMR) AF: 0.287 AC: 4383 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3464

East Asian (EAS) AF: 0.605 AC: 3115 AN: 5150

South Asian (SAS) AF: 0.265 AC: 1272 AN: 4808

European-Finnish (FIN) AF: 0.317 AC: 3331 AN: 10510

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.232 AC: 15770 AN: 67962

Other (OTH) AF: 0.202 AC: 426 AN: 2106

Alfa AF: 0.218 Hom.: 1559

Bravo AF: 0.214

Asia WGS AF: 0.365 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.57
DANN	Benign	0.45
PhyloP100		-0.20
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: rs9390366; hg19: chr6-100864938;