dbSNP rs148528914: SMIM29:p.Gly130Asp (chr6-34246605-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000636500.1(SMIM29):c.389G>A(p.Gly130Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

SMIM29
ENST00000636500.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0460

Publications

0 publications found

Variant links:

Genes affected

SMIM29 (HGNC:1340): (small integral membrane protein 29) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM29 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000636500.1, 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05400598).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636500.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SMIM29	NM_001008703.4	MANE Select	c.*198G>A	3_prime_UTR	Exon 5 of 5	NP_001008703.2	Q86T20-1
SMIM29	NM_178508.6		c.*198G>A	3_prime_UTR	Exon 5 of 5	NP_848603.3	Q86T20-1
SMIM29	NM_001008704.4		c.*198G>A	3_prime_UTR	Exon 5 of 5	NP_001008704.2	Q86T20-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMIM29	ENST00000636500.1	TSL:1	c.389G>A	p.Gly130Asp	missense	Exon 5 of 5	ENSP00000489784.1	A0A2U3TZT1
SMIM29	ENST00000476320.6	TSL:2 MANE Select	c.*198G>A		3_prime_UTR	Exon 5 of 5	ENSP00000417604.2	Q86T20-1
SMIM29	ENST00000481533.5	TSL:1	c.*198G>A		3_prime_UTR	Exon 5 of 5	ENSP00000418062.2	Q86T20-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD2 exomes

AF:

0.0000561

AC:

AN:

249720

AF XY:

0.0000444

show subpopulations

Gnomad AFR exome

AF:

0.000740

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1461002

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726704

show subpopulations

African (AFR)

AF:

0.000896

AC:

AN:

33472

American (AMR)

AF:

0.0000448

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111608

Other (OTH)

AF:

0.0000497

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000191

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.000676

AC:

AN:

41434

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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:

0.000134

Hom.:

Bravo

AF:

0.000287

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.42

CADD

Benign

6.2

(source)

DANN

Benign

0.93

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.43

M_CAP

Benign

0.0017

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.1

PhyloP100

-0.046

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.064

Mutation Taster

=100/0

polymorphism

(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

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