Genetic Variant SAMD3:p.Gly514Glu (chr6-130144542-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 NM_001017373.4(SAMD3):c.1541G>A(p.Gly514Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,613,842 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000062 ( 1 hom. )

Consequence

SAMD3
NM_001017373.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.115

Publications

2 publications found

Variant links:

Genes affected

SAMD3 (HGNC:21574): (sterile alpha motif domain containing 3)

SAMD3 links:

ENSG00000227678 (HGNC:):

ENSG00000227678 links:

Genome browser will be placed here

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=0.026987761).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017373.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD3	NM_001017373.4	MANE Select	c.1541G>A	p.Gly514Glu	missense	Exon 12 of 12	NP_001017373.2	Q8N6K7-1
SAMD3	NM_001277185.2		c.1613G>A	p.Gly538Glu	missense	Exon 11 of 11	NP_001264114.1	Q8N6K7-3
SAMD3	NM_001258275.3		c.1541G>A	p.Gly514Glu	missense	Exon 14 of 14	NP_001245204.1	Q8N6K7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD3	ENST00000439090.7	TSL:2 MANE Select	c.1541G>A	p.Gly514Glu	missense	Exon 12 of 12	ENSP00000403565.2	Q8N6K7-1
SAMD3	ENST00000457563.6	TSL:2	c.1613G>A	p.Gly538Glu	missense	Exon 11 of 11	ENSP00000402092.2	Q8N6K7-3
SAMD3	ENST00000368134.6	TSL:2	c.1541G>A	p.Gly514Glu	missense	Exon 14 of 14	ENSP00000357116.2	Q8N6K7-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000128

AC:

AN:

250822

AF XY:

0.000111

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.0000616

AC:

AN:

1461646

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.000268

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.000880

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

1111888

Other (OTH)

AF:

0.000298

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000657

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41436

American (AMR)

AF:

0.000196

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000135

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

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

0.096

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.026

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.54

M_CAP

Benign

0.0035

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.12

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.070

REVEL

Benign

0.015

Sift

Benign

0.076

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.044

MutPred

0.21

Loss of loop (P = 0.0203)

MVP

0.33

MPC

0.035

ClinPred

0.021

GERP RS

1.5

Varity_R

0.034

gMVP

0.27

Mutation Taster

=98/2

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over