chr6-100406088-C-T

Variant names:

• chr6-100406088-C-T
• rs3798508
• NM_005068.3:c.1168-12199G>A

Variant summary

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

The NM_005068.3(SIM1):​c.1168-12199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,180 control chromosomes in the GnomAD database, including 2,495 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 0.16 (2495 hom., cov: 32)
• Consequence: SIM1 NM_005068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIM1	NM_005068.3	MANE Select	c.1168-12199G>A		intron	N/A	NP_005059.2
	SIM1	NM_001374769.1		c.1168-12199G>A		intron	N/A	NP_001361698.1
	SIM1-AS1	NR_187148.1		n.890+11713C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIM1	ENST00000369208.8	TSL:1 MANE Select	c.1168-12199G>A		intron	N/A	ENSP00000358210.4
	SIM1	ENST00000262901.4	TSL:1	c.1168-12199G>A		intron	N/A	ENSP00000262901.4

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24752 AN: 152062 Hom.: 2498 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.163 AC: 24750 AN: 152180 Hom.: 2495 Cov.: 32 AF XY: 0.166 AC XY: 12320 AN XY: 74396

African (AFR) AF: 0.0380 AC: 1579 AN: 41548

American (AMR) AF: 0.157 AC: 2399 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3470

East Asian (EAS) AF: 0.177 AC: 917 AN: 5180

South Asian (SAS) AF: 0.192 AC: 928 AN: 4826

European-Finnish (FIN) AF: 0.262 AC: 2772 AN: 10562

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14782 AN: 67996

Other (OTH) AF: 0.175 AC: 369 AN: 2106

Alfa AF: 0.210 Hom.: 2621

Bravo AF: 0.151

Asia WGS AF: 0.148 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.99
DANN	Benign	0.37
PhyloP100		-1.1
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: rs3798508; hg19: chr6-100853964; COSMIC: COSV53490231;