rs3798497

Variant names:

• chr6-100430982-A-G
• rs3798497
• NM_005068.3:c.999-10024T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-100430982-A-G
• chr6-100430982-A-T

Variant summary

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

The NM_005068.3(SIM1):​c.999-10024T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,966 control chromosomes in the GnomAD database, including 7,706 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 0.29 (7706 hom., cov: 31)
• Consequence: SIM1 NM_005068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 1 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=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIM1	NM_005068.3	c.999-10024T>C		intron_variant	Intron 9 of 11	ENST00000369208.8	NP_005059.2
SIM1	NM_001374769.1	c.999-10024T>C		intron_variant	Intron 9 of 11		NP_001361698.1
SIM1-AS1	NR_187148.1	n.1041+3714A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIM1	ENST00000369208.8	c.999-10024T>C		intron_variant	Intron 9 of 11	1	NM_005068.3	ENSP00000358210.4
SIM1	ENST00000262901.4	c.999-10024T>C		intron_variant	Intron 8 of 10	1		ENSP00000262901.4
SIM1-AS1	ENST00000411442.1	n.151+3714A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44657 AN: 151848 Hom.: 7696 Cov.: 31

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.294 AC: 44701 AN: 151966 Hom.: 7706 Cov.: 31 AF XY: 0.295 AC XY: 21891 AN XY: 74278

African (AFR) AF: 0.464 AC: 19220 AN: 41406

American (AMR) AF: 0.341 AC: 5206 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3464

East Asian (EAS) AF: 0.424 AC: 2190 AN: 5160

South Asian (SAS) AF: 0.188 AC: 905 AN: 4810

European-Finnish (FIN) AF: 0.221 AC: 2338 AN: 10590

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.199 AC: 13502 AN: 67954

Other (OTH) AF: 0.260 AC: 549 AN: 2112

Alfa AF: 0.238 Hom.: 950

Bravo AF: 0.316

Asia WGS AF: 0.307 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.6
DANN	Benign	0.77
PhyloP100		1.2
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: rs3798497; hg19: chr6-100878858;