NM_005068.3:c.1167+3728A>C

Variant names:

• chr6-100417062-T-G
• rs9390366
• NM_005068.3:c.1167+3728A>C

Variant summary

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

The NM_005068.3(SIM1):​c.1167+3728A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,946 control chromosomes in the GnomAD database, including 4,423 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 0.22 (4423 hom., cov: 31)
• Consequence: SIM1 NM_005068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIM1	NM_005068.3	c.1167+3728A>C		intron_variant	Intron 10 of 11	ENST00000369208.8	NP_005059.2
SIM1	NM_001374769.1	c.1167+3728A>C		intron_variant	Intron 10 of 11		NP_001361698.1
SIM1-AS1	NR_187148.1	n.891-10056T>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIM1	ENST00000369208.8	c.1167+3728A>C		intron_variant	Intron 10 of 11	1	NM_005068.3	ENSP00000358210.4
SIM1	ENST00000262901.4	c.1167+3728A>C		intron_variant	Intron 9 of 10	1		ENSP00000262901.4

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33053 AN: 151828 Hom.: 4412 Cov.: 31

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.218 AC: 33091 AN: 151946 Hom.: 4423 Cov.: 31 AF XY: 0.226 AC XY: 16741 AN XY: 74224

Gnomad4 AFR AF: 0.0934

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.202

Alfa AF: 0.215 Hom.: 1001

Bravo AF: 0.214

Asia WGS AF: 0.365 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.57
DANN	Benign	0.45

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: rs9390366; hg19: chr6-100864938;