dbSNP rs3761472: SAMM50:p.Asp110Gly (chr22-43972242-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 NM_015380.5(SAMM50):c.329A>G(p.Asp110Gly) variant causes a missense change. The variant allele was found at a frequency of 0.172 in 1,561,102 control chromosomes in the GnomAD database, including 25,689 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 2921 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22768 hom. )

Consequence

SAMM50
NM_015380.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.66

Publications

63 publications found

Variant links:

Genes affected

SAMM50 (HGNC:24276): (SAMM50 sorting and assembly machinery component) This gene encodes a component of the Sorting and Assembly Machinery (SAM) of the mitochondrial outer membrane. The Sam complex functions in the assembly of beta-barrel proteins into the outer mitochondrial membrane.[provided by RefSeq, Jun 2011]

SAMM50 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 (MetaRNN=0.0026952326).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMM50	NM_015380.5 link	c.329A>G	p.Asp110Gly	missense_variant	Exon 5 of 15	ENST00000350028.5	NP_056195.3	Q9Y512

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMM50	ENST00000350028.5 link	c.329A>G	p.Asp110Gly	missense_variant	Exon 5 of 15	1	NM_015380.5	ENSP00000345445.4		Q9Y512
SAMM50	ENST00000493161.1 link	n.511A>G		non_coding_transcript_exon_variant	Exon 5 of 7	3

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28574

AN:

151974

Hom.:

2917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.189

GnomAD2 exomes

AF:

0.207

AC:

46333

AN:

223714

AF XY:

0.202

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.310

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.386

Gnomad FIN exome

AF:

0.227

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.201

GnomAD4 exome

AF:

0.171

AC:

240419

AN:

1409010

Hom.:

22768

Cov.:

AF XY:

0.172

AC XY:

120125

AN XY:

700424

show subpopulations

African (AFR)

AF:

0.170

AC:

5336

AN:

31396

American (AMR)

AF:

0.300

AC:

10391

AN:

34628

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

3246

AN:

24572

East Asian (EAS)

AF:

0.401

AC:

15500

AN:

38624

South Asian (SAS)

AF:

0.192

AC:

14972

AN:

78026

European-Finnish (FIN)

AF:

0.225

AC:

11892

AN:

52752

Middle Eastern (MID)

AF:

0.182

AC:

1018

AN:

5590

European-Non Finnish (NFE)

AF:

0.155

AC:

168241

AN:

1085358

Other (OTH)

AF:

0.169

AC:

9823

AN:

58064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

7907

15815

23722

31630

39537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6110

12220

18330

24440

30550

<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:

0.188

AC:

28585

AN:

152092

Hom.:

2921

Cov.:

AF XY:

0.194

AC XY:

14407

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.170

AC:

7073

AN:

41486

American (AMR)

AF:

0.263

AC:

4018

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

451

AN:

3470

East Asian (EAS)

AF:

0.385

AC:

1991

AN:

5170

South Asian (SAS)

AF:

0.209

AC:

1007

AN:

4822

European-Finnish (FIN)

AF:

0.230

AC:

2430

AN:

10564

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.162

AC:

11006

AN:

67988

Other (OTH)

AF:

0.187

AC:

394

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1192

2384

3576

4768

5960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.175

Hom.:

9754

Bravo

AF:

0.192

TwinsUK

AF:

0.157

AC:

584

ALSPAC

AF:

0.167

AC:

642

ESP6500AA

AF:

0.178

AC:

786

ESP6500EA

AF:

0.156

AC:

1339

ExAC

AF:

0.207

AC:

25125

Asia WGS

AF:

0.270

AC:

936

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

Eigen

Benign

-0.045

Eigen_PC

Benign

0.094

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0027

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

PhyloP100

3.7

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.2

REVEL

Benign

0.080

Sift

Benign

0.21

Sift4G

Benign

0.11

Polyphen

0.010

Vest4

0.080

MPC

0.36

ClinPred

0.019

GERP RS

4.8

Varity_R

0.23

gMVP

0.54

Mutation Taster

=48/52

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over