Genetic Variant SAMD15:p.Lys454Glu (chr14-77378778-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_001010860.4(SAMD15):c.1360A>G(p.Lys454Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,611,202 control chromosomes in the GnomAD database, including 191,651 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K454R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.56 ( 26383 hom., cov: 33)

Exomes 𝑓: 0.47 ( 165268 hom. )

Consequence

SAMD15
NM_001010860.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.861

Publications

31 publications found

Variant links:

Genes affected

SAMD15 (HGNC:18631): (sterile alpha motif domain containing 15)

SAMD15 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=1.1498308E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD15	NM_001010860.4 link	c.1360A>G	p.Lys454Glu	missense_variant	Exon 1 of 3	ENST00000216471.5	NP_001010860.1	Q9P1V8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD15	ENST00000216471.5 link	c.1360A>G	p.Lys454Glu	missense_variant	Exon 1 of 3	2	NM_001010860.4	ENSP00000216471.4		Q9P1V8-1
SAMD15	ENST00000533095.2 link	c.-69-1605A>G		intron_variant	Intron 1 of 2	5		ENSP00000450941.1		G3V2Z3

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

85080

AN:

152024

Hom.:

26339

Cov.:

show subpopulations

Gnomad AFR

AF:

0.829

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.0850

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.550

GnomAD2 exomes

AF:

0.472

AC:

117586

AN:

248956

AF XY:

0.472

show subpopulations

Gnomad AFR exome

AF:

0.836

Gnomad AMR exome

AF:

0.475

Gnomad ASJ exome

AF:

0.493

Gnomad EAS exome

AF:

0.0769

Gnomad FIN exome

AF:

0.468

Gnomad NFE exome

AF:

0.471

Gnomad OTH exome

AF:

0.483

GnomAD4 exome

AF:

0.467

AC:

680851

AN:

1459060

Hom.:

165268

Cov.:

AF XY:

0.469

AC XY:

340082

AN XY:

725828

show subpopulations

African (AFR)

AF:

0.844

AC:

28069

AN:

33238

American (AMR)

AF:

0.473

AC:

20816

AN:

44036

Ashkenazi Jewish (ASJ)

AF:

0.494

AC:

12850

AN:

26028

East Asian (EAS)

AF:

0.0689

AC:

2734

AN:

39682

South Asian (SAS)

AF:

0.517

AC:

44293

AN:

85680

European-Finnish (FIN)

AF:

0.463

AC:

24734

AN:

53374

Middle Eastern (MID)

AF:

0.596

AC:

3428

AN:

5756

European-Non Finnish (NFE)

AF:

0.464

AC:

515058

AN:

1111022

Other (OTH)

AF:

0.479

AC:

28869

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

20960

41920

62880

83840

104800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15298

30596

45894

61192

76490

<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:

0.560

AC:

85178

AN:

152142

Hom.:

26383

Cov.:

AF XY:

0.555

AC XY:

41256

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.829

AC:

34441

AN:

41532

American (AMR)

AF:

0.515

AC:

7869

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

1710

AN:

3468

East Asian (EAS)

AF:

0.0850

AC:

440

AN:

5178

South Asian (SAS)

AF:

0.490

AC:

2365

AN:

4826

European-Finnish (FIN)

AF:

0.460

AC:

4864

AN:

10564

Middle Eastern (MID)

AF:

0.646

AC:

190

AN:

294

European-Non Finnish (NFE)

AF:

0.469

AC:

31865

AN:

67974

Other (OTH)

AF:

0.544

AC:

1147

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1726

3453

5179

6906

8632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<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:

0.501

Hom.:

68161

Bravo

AF:

0.570

TwinsUK

AF:

0.448

AC:

1660

ALSPAC

AF:

0.467

AC:

1798

ESP6500AA

AF:

0.823

AC:

3626

ESP6500EA

AF:

0.468

AC:

4023

ExAC

AF:

0.482

AC:

58516

Asia WGS

AF:

0.316

AC:

1102

AN:

3478

EpiCase

AF:

0.489

EpiControl

AF:

0.487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.18

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.00092

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

-0.86

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.24

REVEL

Benign

0.021

Sift

Benign

0.50

Sift4G

Benign

0.94

Polyphen

0.0

Vest4

0.011

MPC

0.10

ClinPred

0.0041

GERP RS

-2.4

Varity_R

0.041

gMVP

0.025

Mutation Taster

=100/0

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