6-100431775-C-T

Variant names:

• chr6-100431775-C-T
• rs241816
• NM_005068.3:c.999-10817G>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.999-10817G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,986 control chromosomes in the GnomAD database, including 27,053 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 0.59 (27053 hom., cov: 32)
• Consequence: SIM1 NM_005068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIM1	NM_005068.3	c.999-10817G>A		intron_variant	Intron 9 of 11	ENST00000369208.8	NP_005059.2
SIM1	NM_001374769.1	c.999-10817G>A		intron_variant	Intron 9 of 11		NP_001361698.1
SIM1-AS1	NR_187148.1	n.1041+4507C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIM1	ENST00000369208.8	c.999-10817G>A		intron_variant	Intron 9 of 11	1	NM_005068.3	ENSP00000358210.4
SIM1	ENST00000262901.4	c.999-10817G>A		intron_variant	Intron 8 of 10	1		ENSP00000262901.4
SIM1-AS1	ENST00000411442.1	n.151+4507C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89494 AN: 151868 Hom.: 27037 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.589 AC: 89541 AN: 151986 Hom.: 27053 Cov.: 32 AF XY: 0.591 AC XY: 43907 AN XY: 74264

African (AFR) AF: 0.465 AC: 19300 AN: 41472

American (AMR) AF: 0.532 AC: 8121 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2095 AN: 3466

East Asian (EAS) AF: 0.524 AC: 2705 AN: 5164

South Asian (SAS) AF: 0.764 AC: 3678 AN: 4814

European-Finnish (FIN) AF: 0.665 AC: 7009 AN: 10532

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44714 AN: 67970

Other (OTH) AF: 0.585 AC: 1234 AN: 2110

Alfa AF: 0.627 Hom.: 55690

Bravo AF: 0.566

Asia WGS AF: 0.626 AC: 2179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.49
DANN	Benign	0.39
PhyloP100		-0.38
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: rs241816; hg19: chr6-100879651; COSMIC: COSV53490266;