Genetic Variant SMIM26:c.-67A>T (chr20-18567412-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39

Publications

5 publications found

Variant links:

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]

SMIM26 links:

ENSG00000284776 (HGNC:):

ENSG00000284776 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMIM26	NM_001348957.2 link	c.-67A>T		upstream_gene_variant		ENST00000411646.2	NP_001335886.1
SMIM26	NM_001348958.2 link	c.-67A>T		upstream_gene_variant			NP_001335887.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMIM26	ENST00000435844.3 link	c.-67A>T	5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000485491.1	A0A096LPB2
SMIM26	ENST00000411646.2 link	c.-67A>T	upstream_gene_variant		1	NM_001348957.2	ENSP00000485316.2	A0A096LP01
ENSG00000284776	ENST00000618693.4 link	c.-67A>T	upstream_gene_variant		5		ENSP00000482916.1	A0A087WZV9
SMIM26	ENST00000608034.1 link	c.-67A>T	upstream_gene_variant		3		ENSP00000485501.1	A0A096LPB8

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

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:

AN:

548012

Hom.:

Cov.:

AF XY:

0.00000337

AC XY:

AN XY:

296426

show subpopulations

African (AFR)

AF:

0.0000634

AC:

AN:

15766

American (AMR)

AF:

0.00

AC:

AN:

34632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19956

East Asian (EAS)

AF:

0.00

AC:

AN:

32064

South Asian (SAS)

AF:

0.00

AC:

AN:

62562

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3822

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

315230

Other (OTH)

AF:

0.00

AC:

AN:

30476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.34

(source)

DANN

Benign

0.56

PhyloP100

-1.4

PromoterAI

-0.00080

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over