Genetic Variant SAMD3:p.Val513Ile (chr6-130144546-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.1537G>A(p.Val513Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00029 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SAMD3
NM_001017373.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.210

Publications

0 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=0.011746317).

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.1537G>A	p.Val513Ile	missense	Exon 12 of 12	NP_001017373.2	Q8N6K7-1
SAMD3	NM_001277185.2		c.1609G>A	p.Val537Ile	missense	Exon 11 of 11	NP_001264114.1	Q8N6K7-3
SAMD3	NM_001258275.3		c.1537G>A	p.Val513Ile	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.1537G>A	p.Val513Ile	missense	Exon 12 of 12	ENSP00000403565.2	Q8N6K7-1
SAMD3	ENST00000457563.6	TSL:2	c.1609G>A	p.Val537Ile	missense	Exon 11 of 11	ENSP00000402092.2	Q8N6K7-3
SAMD3	ENST00000368134.6	TSL:2	c.1537G>A	p.Val513Ile	missense	Exon 14 of 14	ENSP00000357116.2	Q8N6K7-1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

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:

0.0000718

AC:

AN:

250832

AF XY:

0.0000590

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.0000580

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:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461664

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.000747

AC:

AN:

33466

American (AMR)

AF:

0.0000671

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111914

Other (OTH)

AF:

0.0000331

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.000289

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

41564

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.000613

Hom.:

Bravo

AF:

0.000314

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

0.074

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.4

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.023

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.60

M_CAP

Benign

0.0031

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

PhyloP100

-0.21

PrimateAI

Benign

0.24

PROVEAN

Benign

0.090

REVEL

Benign

0.026

Sift

Benign

0.47

Sift4G

Benign

0.53

Polyphen

0.0

Vest4

0.039

MVP

0.32

MPC

0.027

ClinPred

0.0031

GERP RS

1.1

Varity_R

0.023

gMVP

0.099

Mutation Taster

=93/7

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