Genetic Variant SMIM23:c.3+2476C>A (chr5-171776434-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The XM_011534623.2(SMIM23):c.3+2476C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,072 control chromosomes in the GnomAD database, including 3,726 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 0.21 ( 3726 hom., cov: 32)

Consequence

SMIM23
XM_011534623.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.539

Publications

39 publications found

Variant links:

Genes affected

SMIM23 (HGNC:34440): (small integral membrane protein 23) Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM23 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=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMIM23	XM_011534623.2 link	c.3+2476C>A		intron_variant	Intron 1 of 3		XP_011532925.1
SMIM23	XM_011534624.2 link	c.3+2476C>A		intron_variant	Intron 2 of 4		XP_011532926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31413

AN:

151954

Hom.:

3725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0954

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.215

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.207

AC:

31414

AN:

152072

Hom.:

3726

Cov.:

AF XY:

0.210

AC XY:

15643

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.0950

AC:

3945

AN:

41512

American (AMR)

AF:

0.243

AC:

3720

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1051

AN:

3464

East Asian (EAS)

AF:

0.398

AC:

2047

AN:

5144

South Asian (SAS)

AF:

0.141

AC:

677

AN:

4814

European-Finnish (FIN)

AF:

0.284

AC:

2996

AN:

10544

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.240

AC:

16308

AN:

67992

Other (OTH)

AF:

0.218

AC:

460

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1233

2467

3700

4934

6167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.230

Hom.:

8967

Bravo

AF:

0.203

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.7

(source)

DANN

Benign

0.80

PhyloP100

-0.54

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