dbSNP rs12624935: SMIM26:c.-67A>G (chr20-18567412-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

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

new If you want to explore the variant's impact on the transcript ENST00000435844.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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>G		upstream_gene	N/A	NP_001335886.1	A0A096LP01-1
	SMIM26	NM_001348958.2		c.-67A>G		upstream_gene	N/A	NP_001335887.1	A0A096LP01-2

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19063

AN:

152100

Hom.:

1304

Cov.:

show subpopulations

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.:

AF XY:

0.114

AC XY:

33785

AN XY:

296378

show subpopulations

African (AFR)

AF:

0.115

AC:

1807

AN:

15764

American (AMR)

AF:

0.203

AC:

7023

AN:

34624

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

3002

AN:

19952

East Asian (EAS)

AF:

0.146

AC:

4677

AN:

32058

South Asian (SAS)

AF:

0.0463

AC:

2897

AN:

62560

European-Finnish (FIN)

AF:

0.127

AC:

4257

AN:

33500

Middle Eastern (MID)

AF:

0.141

AC:

537

AN:

3820

European-Non Finnish (NFE)

AF:

0.119

AC:

37660

AN:

315178

Other (OTH)

AF:

0.121

AC:

3687

AN:

30470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2966

5932

8898

11864

14830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

250

500

750

1000

1250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.125

AC:

19065

AN:

152218

Hom.:

1303

Cov.:

AF XY:

0.126

AC XY:

9377

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.115

AC:

4765

AN:

41530

American (AMR)

AF:

0.183

AC:

2801

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

574

AN:

3470

East Asian (EAS)

AF:

0.160

AC:

830

AN:

5178

South Asian (SAS)

AF:

0.0414

AC:

200

AN:

4828

European-Finnish (FIN)

AF:

0.131

AC:

1385

AN:

10602

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.118

AC:

8014

AN:

68002

Other (OTH)

AF:

0.143

AC:

302

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

891

1782

2672

3563

4454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<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:

0.0880

Hom.:

165

Bravo

AF:

0.133

Asia WGS

AF:

0.0990

AC:

343

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.40

(source)

DANN

Benign

0.39

PhyloP100

-1.4

PromoterAI

-0.084

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over