Genetic Variant SMIM21:c.129+55G>C (chr18-75427380-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001037331.3(SMIM21):c.129+55G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,580,254 control chromosomes in the GnomAD database, including 92,763 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 0.28 ( 6718 hom., cov: 32)

Exomes 𝑓: 0.34 ( 86045 hom. )

Consequence

SMIM21
NM_001037331.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0790

Publications

10 publications found

Variant links:

Genes affected

SMIM21 (HGNC:27598): (small integral membrane protein 21) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM21 links:

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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=-0.98).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037331.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM21	NM_001037331.3	MANE Select	c.129+55G>C		intron	N/A	NP_001032408.1
	SMIM21	NM_001303482.2		c.129+55G>C		intron	N/A	NP_001290411.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMIM21	ENST00000579022.5	TSL:1 MANE Select	c.129+55G>C	intron	N/A	ENSP00000462106.1
SMIM21	ENST00000584508.1	TSL:1	c.129+55G>C	intron	N/A	ENSP00000462572.1
SMIM21	ENST00000382638.3	TSL:1	c.129+55G>C	intron	N/A	ENSP00000372083.3

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

43052

AN:

151982

Hom.:

6726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.423

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.315

GnomAD4 exome

AF:

0.343

AC:

489855

AN:

1428154

Hom.:

86045

AF XY:

0.344

AC XY:

243305

AN XY:

707624

show subpopulations

African (AFR)

AF:

0.143

AC:

4734

AN:

33058

American (AMR)

AF:

0.213

AC:

9224

AN:

43326

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

10309

AN:

24108

East Asian (EAS)

AF:

0.243

AC:

9557

AN:

39330

South Asian (SAS)

AF:

0.301

AC:

23880

AN:

79392

European-Finnish (FIN)

AF:

0.378

AC:

19471

AN:

51500

Middle Eastern (MID)

AF:

0.357

AC:

2009

AN:

5628

European-Non Finnish (NFE)

AF:

0.358

AC:

390855

AN:

1092750

Other (OTH)

AF:

0.336

AC:

19816

AN:

59062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

15271

30543

45814

61086

76357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12374

24748

37122

49496

61870

<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:

0.283

AC:

43041

AN:

152100

Hom.:

6718

Cov.:

AF XY:

0.282

AC XY:

21003

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.148

AC:

6121

AN:

41486

American (AMR)

AF:

0.240

AC:

3660

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.423

AC:

1469

AN:

3470

East Asian (EAS)

AF:

0.197

AC:

1023

AN:

5184

South Asian (SAS)

AF:

0.284

AC:

1368

AN:

4822

European-Finnish (FIN)

AF:

0.377

AC:

3987

AN:

10584

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.359

AC:

24419

AN:

67970

Other (OTH)

AF:

0.315

AC:

665

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1600

3200

4801

6401

8001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.207

Hom.:

485

Bravo

AF:

0.263

Asia WGS

AF:

0.252

AC:

877

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

2.4

(source)

DANN

Benign

0.50

PhyloP100

-0.079

PromoterAI

0.016

Neutral

(source)

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