6-100396392-T-C

Variant names:

• chr6-100396392-T-C
• rs3798514
• NM_005068.3:c.1168-2503A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005068.3(SIM1):​c.1168-2503A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,002 control chromosomes in the GnomAD database, including 1,047 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 0.12 (1047 hom., cov: 32)
• Consequence: SIM1 NM_005068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 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.1168-2503A>G		intron	N/A	NP_005059.2
	SIM1	NM_001374769.1		c.1168-2503A>G		intron	N/A	NP_001361698.1
	SIM1-AS1	NR_187148.1		n.890+2017T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIM1	ENST00000369208.8	TSL:1 MANE Select	c.1168-2503A>G		intron	N/A	ENSP00000358210.4
	SIM1	ENST00000262901.4	TSL:1	c.1168-2503A>G		intron	N/A	ENSP00000262901.4

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17690 AN: 151884 Hom.: 1035 Cov.: 32

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.0606

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0733

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.117 AC: 17709 AN: 152002 Hom.: 1047 Cov.: 32 AF XY: 0.114 AC XY: 8480 AN XY: 74294

African (AFR) AF: 0.0945 AC: 3914 AN: 41438

American (AMR) AF: 0.135 AC: 2055 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3472

East Asian (EAS) AF: 0.152 AC: 781 AN: 5152

South Asian (SAS) AF: 0.0726 AC: 349 AN: 4810

European-Finnish (FIN) AF: 0.0883 AC: 932 AN: 10558

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8837 AN: 67996

Other (OTH) AF: 0.134 AC: 282 AN: 2104

Alfa AF: 0.124 Hom.: 607

Bravo AF: 0.119

Asia WGS AF: 0.142 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Benign	0.76
PhyloP100		0.27
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: rs3798514; hg19: chr6-100844268;