rs14103

Positions:

• chr1-34855641-A-C

Variant summary

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

The NM_138428.6(SMIM12):​c.*58T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 1,613,994 control chromosomes in the GnomAD database, including 5,272 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 0.076 (467 hom., cov: 33)
  • Exomes 𝑓: 0.077 (4805 hom.)
• Consequence: SMIM12 NM_138428.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMIM12	NM_138428.6	c.*58T>G		3_prime_UTR_variant	2/2	ENST00000521580.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMIM12	ENST00000521580.3	c.*58T>G		3_prime_UTR_variant	2/2	1	NM_138428.6	P1

Frequencies

GnomAD3 genomes AF: 0.0762 AC: 11593 AN: 152160 Hom.: 464 Cov.: 33

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0792

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0880

GnomAD3 exomes AF: 0.0771 AC: 19332 AN: 250602 Hom.: 892 AF XY: 0.0802 AC XY: 10887 AN XY: 135702

Gnomad AFR exome AF: 0.0825

Gnomad AMR exome AF: 0.0418

Gnomad ASJ exome AF: 0.0804

Gnomad EAS exome AF: 0.116

Gnomad SAS exome AF: 0.114

Gnomad FIN exome AF: 0.0530

Gnomad NFE exome AF: 0.0749

Gnomad OTH exome AF: 0.0822

GnomAD4 exome AF: 0.0771 AC: 112745 AN: 1461716 Hom.: 4805 Cov.: 32 AF XY: 0.0786 AC XY: 57125 AN XY: 727148

Gnomad4 AFR exome AF: 0.0811

Gnomad4 AMR exome AF: 0.0434

Gnomad4 ASJ exome AF: 0.0803

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.0535

Gnomad4 NFE exome AF: 0.0744

Gnomad4 OTH exome AF: 0.0840

GnomAD4 genome AF: 0.0763 AC: 11618 AN: 152278 Hom.: 467 Cov.: 33 AF XY: 0.0762 AC XY: 5677 AN XY: 74472

Gnomad4 AFR AF: 0.0803

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.0792

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0537

Gnomad4 NFE AF: 0.0756

Gnomad4 OTH AF: 0.0876

Alfa AF: 0.0769 Hom.: 819

Bravo AF: 0.0760

Asia WGS AF: 0.121 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.4
DANN	Benign	0.67

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: rs14103; hg19: chr1-35321242;