rs3798514

chr6-100396392-T-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIM1	NM_005068.3	c.1168-2503A>G		intron_variant		ENST00000369208.8
SIM1-AS1	XR_942815.4	n.890+2017T>C		intron_variant, non_coding_transcript_variant
SIM1	NM_001374769.1	c.1168-2503A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIM1	ENST00000369208.8	c.1168-2503A>G		intron_variant		1	NM_005068.3	P1
SIM1	ENST00000262901.4	c.1168-2503A>G		intron_variant		1		P1

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

Gnomad4 AFR AF: 0.0945

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.0726

Gnomad4 FIN AF: 0.0883

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.134

Alfa AF: 0.124 Hom.: 540

Bravo AF: 0.119

Asia WGS AF: 0.142 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	14
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs3798514; hg19: chr6-100844268;