rs12624935

Positions:

• chr20-18567412-A-G
• chr20-18567412-A-T

Variant summary

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

The ENST00000435844.3(SMIM26):​c.-67A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 700,144 control chromosomes in the GnomAD database, including 5,674 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 0.13 (1303 hom., cov: 33)
  • Exomes 𝑓: 0.12 (4371 hom.)
• Consequence: SMIM26 ENST00000435844.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

Genes affected

SMIM26 (HGNC:43430): (small integral membrane protein 26) 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 (AMR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMIM26	NM_001348957.2			upstream_gene_variant		ENST00000411646.2	NP_001335886.1
SMIM26	NM_001348958.2			upstream_gene_variant			NP_001335887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMIM26	ENST00000435844.3	c.-67A>G		5_prime_UTR_variant	1/2	1		ENSP00000485491	A2
SMIM26	ENST00000411646.2			upstream_gene_variant		1	NM_001348957.2	ENSP00000485316	P4
SMIM26	ENST00000608034.1			upstream_gene_variant		3		ENSP00000485501	A2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19063 AN: 152100 Hom.: 1304 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.120 AC: 65547 AN: 547926 Hom.: 4371 Cov.: 0 AF XY: 0.114 AC XY: 33785 AN XY: 296378

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.146

Gnomad4 SAS exome AF: 0.0463

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.125 AC: 19065 AN: 152218 Hom.: 1303 Cov.: 33 AF XY: 0.126 AC XY: 9377 AN XY: 74436

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.0414

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.143

Alfa AF: 0.0873 Hom.: 160

Bravo AF: 0.133

Asia WGS AF: 0.0990 AC: 343 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	0.40
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12624935; hg19: chr20-18548056;