Genetic Variant NM_015380.5:c.329A>G (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

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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