Genetic Variant NM_138428.6:c.*58T>G (chr1-34855641-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_138428.6(SMIM12):c.*58T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 1,613,994 control chromosomes in the GnomAD database, including 5,272 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 0.076 ( 467 hom., cov: 33)

Exomes 𝑓: 0.077 ( 4805 hom. )

Consequence

SMIM12
NM_138428.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0900

Publications

12 publications found

Variant links:

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]

SMIM12 links:

Genome browser will be placed here

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 (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138428.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SMIM12	NM_138428.6	MANE Select	c.*58T>G	3_prime_UTR	Exon 2 of 2	NP_612437.3
SMIM12	NM_001164824.2		c.*58T>G	3_prime_UTR	Exon 3 of 3	NP_001158296.1	Q96EX1
SMIM12	NM_001164825.2		c.*58T>G	3_prime_UTR	Exon 2 of 2	NP_001158297.1	Q96EX1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SMIM12	ENST00000521580.3	TSL:1 MANE Select	c.*58T>G	3_prime_UTR	Exon 2 of 2	ENSP00000428585.1	Q96EX1
SMIM12	ENST00000446026.1	TSL:1	c.*58T>G	3_prime_UTR	Exon 2 of 2	ENSP00000430285.1	Q96EX1
SMIM12	ENST00000426886.1	TSL:1	n.207+130T>G	intron	N/A	ENSP00000429902.1	E5RH51

Frequencies

GnomAD3 genomes

AF:

0.0762

AC:

11593

AN:

152160

Hom.:

464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0800

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.0560

Gnomad ASJ

AF:

0.0792

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.0537

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0756

Gnomad OTH

AF:

0.0880

GnomAD2 exomes

AF:

0.0771

AC:

19332

AN:

250602

AF XY:

0.0802

show subpopulations

Gnomad AFR exome

AF:

0.0825

Gnomad AMR exome

AF:

0.0418

Gnomad ASJ exome

AF:

0.0804

Gnomad EAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.0530

Gnomad NFE exome

AF:

0.0749

Gnomad OTH exome

AF:

0.0822

GnomAD4 exome

AF:

0.0771

AC:

112745

AN:

1461716

Hom.:

4805

Cov.:

AF XY:

0.0786

AC XY:

57125

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.0811

AC:

2716

AN:

33478

American (AMR)

AF:

0.0434

AC:

1939

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0803

AC:

2099

AN:

26134

East Asian (EAS)

AF:

0.130

AC:

5172

AN:

39700

South Asian (SAS)

AF:

0.112

AC:

9644

AN:

86200

European-Finnish (FIN)

AF:

0.0535

AC:

2859

AN:

53416

Middle Eastern (MID)

AF:

0.0860

AC:

496

AN:

5768

European-Non Finnish (NFE)

AF:

0.0744

AC:

82745

AN:

1111908

Other (OTH)

AF:

0.0840

AC:

5075

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

6535

13069

19604

26138

32673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3130

6260

9390

12520

15650

<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:

0.0763

AC:

11618

AN:

152278

Hom.:

467

Cov.:

AF XY:

0.0762

AC XY:

5677

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0803

AC:

3336

AN:

41556

American (AMR)

AF:

0.0559

AC:

855

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0792

AC:

275

AN:

3472

East Asian (EAS)

AF:

0.128

AC:

663

AN:

5186

South Asian (SAS)

AF:

0.111

AC:

534

AN:

4820

European-Finnish (FIN)

AF:

0.0537

AC:

570

AN:

10616

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0756

AC:

5142

AN:

68014

Other (OTH)

AF:

0.0876

AC:

185

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

556

1112

1667

2223

2779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.0765

Hom.:

1682

Bravo

AF:

0.0760

Asia WGS

AF:

0.121

AC:

418

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

3.4

(source)

DANN

Benign

0.67

PhyloP100

0.090

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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