rs3822980

Positions:

• chr6-100426062-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005068.3(SIM1):​c.999-5104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 152,300 control chromosomes in the GnomAD database, including 82 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 0.011 (82 hom., cov: 32)
• Consequence: SIM1 NM_005068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIM1	NM_005068.3	c.999-5104C>T		intron_variant		ENST00000369208.8
SIM1-AS1	XR_942815.4	n.891-1056G>A		intron_variant, non_coding_transcript_variant
SIM1	NM_001374769.1	c.999-5104C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIM1	ENST00000369208.8	c.999-5104C>T		intron_variant		1	NM_005068.3	P1
SIM1	ENST00000262901.4	c.999-5104C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1751 AN: 152182 Hom.: 82 Cov.: 32

Gnomad AFR AF: 0.00347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0134

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

GnomAD4 genome AF: 0.0115 AC: 1745 AN: 152300 Hom.: 82 Cov.: 32 AF XY: 0.0129 AC XY: 960 AN XY: 74464

Gnomad4 AFR AF: 0.00346

Gnomad4 AMR AF: 0.0523

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00450 Hom.: 3

Bravo AF: 0.0161

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.0
DANN	Benign	0.69

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: rs3822980; hg19: chr6-100873938;