1-34856902-T-C

Position:

• chr1-34856902-T-C

Variant summary

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

The NM_138428.6(SMIM12):​c.-5-920A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,142 control chromosomes in the GnomAD database, including 57,473 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 0.87 (57473 hom., cov: 31)
• Consequence: SMIM12 NM_138428.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMIM12	NM_138428.6	c.-5-920A>G		intron_variant		ENST00000521580.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMIM12	ENST00000521580.3	c.-5-920A>G		intron_variant		1	NM_138428.6	P1

Frequencies

GnomAD3 genomes AF: 0.868 AC: 131993 AN: 152024 Hom.: 57434 Cov.: 31

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.868 AC: 132087 AN: 152142 Hom.: 57473 Cov.: 31 AF XY: 0.869 AC XY: 64659 AN XY: 74388

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.901

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.846

Gnomad4 NFE AF: 0.885

Gnomad4 OTH AF: 0.881

Alfa AF: 0.882 Hom.: 78081

Bravo AF: 0.867

Asia WGS AF: 0.967 AC: 3363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.8
DANN	Benign	0.46

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: rs4653107; hg19: chr1-35322503;