20-18567412-A-T

Variant names:

• chr20-18567412-A-T
• rs12624935
• ENST00000435844.3:c.-67A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000435844.3(SMIM26):​c.-67A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000571 in 700,136 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: SMIM26 ENST00000435844.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 5 publications found

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]

ENSG00000284776 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000435844.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM26	NM_001348957.2	MANE Select	c.-67A>T		upstream_gene	N/A	NP_001335886.1	A0A096LP01-1
	SMIM26	NM_001348958.2		c.-67A>T		upstream_gene	N/A	NP_001335887.1	A0A096LP01-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM26	ENST00000435844.3	TSL:1	c.-67A>T		5_prime_UTR	Exon 1 of 2	ENSP00000485491.1	A0A096LP01-2
	SMIM26	ENST00000411646.2	TSL:1 MANE Select	c.-67A>T		upstream_gene	N/A	ENSP00000485316.2	A0A096LP01-1
	ENSG00000284776	ENST00000618693.4	TSL:5	c.-67A>T		upstream_gene	N/A	ENSP00000482916.1	A0A087WZV9

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152124 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 1 AN: 548012 Hom.: 0 Cov.: 0 AF XY: 0.00000337 AC XY: 1 AN XY: 296426

African (AFR) AF: 0.0000634 AC: 1 AN: 15766

American (AMR) AF: 0.00 AC: 0 AN: 34632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19956

East Asian (EAS) AF: 0.00 AC: 0 AN: 32064

South Asian (SAS) AF: 0.00 AC: 0 AN: 62562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3822

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 315230

Other (OTH) AF: 0.00 AC: 0 AN: 30476

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152124 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74322

African (AFR) AF: 0.0000724 AC: 3 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.34
DANN	Benign	0.56
PhyloP100		-1.4
PromoterAI		-0.00080	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12624935;

hg19: chr20-18548056;