6-100430391-C-T

Variant names:

• chr6-100430391-C-T
• rs3798498
• NM_005068.3:c.999-9433G>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.999-9433G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,952 control chromosomes in the GnomAD database, including 21,436 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 0.52 (21436 hom., cov: 32)
• Consequence: SIM1 NM_005068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIM1	NM_005068.3	c.999-9433G>A		intron_variant	Intron 9 of 11	ENST00000369208.8	NP_005059.2
SIM1	NM_001374769.1	c.999-9433G>A		intron_variant	Intron 9 of 11		NP_001361698.1
SIM1-AS1	NR_187148.1	n.1041+3123C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIM1	ENST00000369208.8	c.999-9433G>A		intron_variant	Intron 9 of 11	1	NM_005068.3	ENSP00000358210.4
SIM1	ENST00000262901.4	c.999-9433G>A		intron_variant	Intron 8 of 10	1		ENSP00000262901.4
SIM1-AS1	ENST00000411442.1	n.151+3123C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78574 AN: 151834 Hom.: 21433 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.517 AC: 78588 AN: 151952 Hom.: 21436 Cov.: 32 AF XY: 0.518 AC XY: 38478 AN XY: 74262

African (AFR) AF: 0.357 AC: 14777 AN: 41396

American (AMR) AF: 0.444 AC: 6778 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1976 AN: 3468

East Asian (EAS) AF: 0.364 AC: 1883 AN: 5170

South Asian (SAS) AF: 0.672 AC: 3241 AN: 4822

European-Finnish (FIN) AF: 0.635 AC: 6709 AN: 10562

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41450 AN: 67958

Other (OTH) AF: 0.525 AC: 1107 AN: 2110

Alfa AF: 0.549 Hom.: 30808

Bravo AF: 0.487

Asia WGS AF: 0.487 AC: 1696 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.77
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3798498; hg19: chr6-100878267; COSMIC: COSV53490258;