Genetic Variant SAMD3:p.Arg228Cys (chr6-130175981-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001017373.4(SAMD3):c.682C>T(p.Arg228Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000354 in 1,612,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

SAMD3
NM_001017373.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

Publications

5 publications found

Variant links:

Genes affected

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

SAMD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.786

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.682C>T	p.Arg228Cys	missense	Exon 8 of 12	NP_001017373.2	Q8N6K7-1
SAMD3	NM_001277185.2		c.754C>T	p.Arg252Cys	missense	Exon 7 of 11	NP_001264114.1	Q8N6K7-3
SAMD3	NM_001258275.3		c.682C>T	p.Arg228Cys	missense	Exon 10 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.682C>T	p.Arg228Cys	missense	Exon 8 of 12	ENSP00000403565.2	Q8N6K7-1
SAMD3	ENST00000533296.5	TSL:1	n.1359C>T		non_coding_transcript_exon	Exon 7 of 7
SAMD3	ENST00000457563.6	TSL:2	c.754C>T	p.Arg252Cys	missense	Exon 7 of 11	ENSP00000402092.2	Q8N6K7-3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000281

AC:

AN:

249096

AF XY:

0.0000297

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000587

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1460164

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33408

American (AMR)

AF:

0.0000450

AC:

AN:

44424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39608

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000351

AC:

AN:

1111382

Other (OTH)

AF:

0.0000994

AC:

AN:

60332

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

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:

0.0000460

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41418

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.568

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:

0.000107

Hom.:

Bravo

AF:

0.0000604

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

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

Pathogenic

0.76

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.038

MetaRNN

Pathogenic

0.79

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.9

PhyloP100

4.8

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.94

MutPred

0.61

Gain of methylation at K230 (P = 0.0508)

MVP

0.83

MPC

0.26

ClinPred

0.96

GERP RS

5.7

Varity_R

0.39

gMVP

0.72

Mutation Taster

=82/18

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