rs10489656

Positions:

• chr1-34765777-A-G

Variant summary

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

The ENST00000426886.1(SMIM12):​c.208-47368T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,058 control chromosomes in the GnomAD database, including 9,456 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 0.35 (9456 hom., cov: 32)
• Consequence: SMIM12 ENST00000426886.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

Genes affected

SMIM12 (HGNC:25154): (small integral membrane protein 12) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMIM12	ENST00000426886.1	c.208-47368T>C		intron_variant, NMD_transcript_variant		1
	ENST00000542839.1	n.111-3902T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52841 AN: 151940 Hom.: 9431 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.348 AC: 52915 AN: 152058 Hom.: 9456 Cov.: 32 AF XY: 0.345 AC XY: 25635 AN XY: 74328

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.345

Alfa AF: 0.342 Hom.: 11465

Bravo AF: 0.341

Asia WGS AF: 0.255 AC: 885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.4
DANN	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10489656; hg19: chr1-35231378; COSMIC: COSV59768812;