Genetic Variant SAMD14:c.*2373G>A (chr17-50110520-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001257359.2(SAMD14):c.*2373G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 155,112 control chromosomes in the GnomAD database, including 25,308 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 24818 hom., cov: 32)

Exomes 𝑓: 0.54 ( 490 hom. )

Consequence

SAMD14
NM_001257359.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.942

Publications

13 publications found

Variant links:

Genes affected

SAMD14 (HGNC:27312): (sterile alpha motif domain containing 14) Predicted to enable actin filament binding activity. Predicted to be involved in actin filament organization; calcium-mediated signaling; and neuron projection development. Predicted to be active in several cellular components, including actin cytoskeleton; dendrite; and postsynaptic density. [provided by Alliance of Genome Resources, Apr 2022]

SAMD14 links:

PDK2 (HGNC:8810): (pyruvate dehydrogenase kinase 2) This gene encodes a member of the pyruvate dehydrogenase kinase family. The encoded protein phosphorylates pyruvate dehydrogenase, down-regulating the activity of the mitochondrial pyruvate dehydrogenase complex. Overexpression of this gene may play a role in both cancer and diabetes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

PDK2 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 (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD14	NM_001257359.2 link	c.*2373G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000330175.9	NP_001244288.1	Q8IZD0-1
PDK2	NM_002611.5 link	c.*423C>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000503176.6	NP_002602.2	Q15119-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SAMD14	ENST00000330175.9 link	c.*2373G>A	3_prime_UTR_variant	Exon 10 of 10	1	NM_001257359.2	ENSP00000329144.4	Q8IZD0-1
PDK2	ENST00000503176.6 link	c.*423C>T	3_prime_UTR_variant	Exon 11 of 11	1	NM_002611.5	ENSP00000420927.1	Q15119-1
PDK2	ENST00000007708.7 link	c.*423C>T	3_prime_UTR_variant	Exon 12 of 12	2		ENSP00000007708.3	Q15119-2
PDK2	ENST00000614357.4 link	c.*423C>T	3_prime_UTR_variant	Exon 11 of 11	5		ENSP00000481915.1	Q15119-2

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86496

AN:

151792

Hom.:

24797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.579

Gnomad AMR

AF:

0.517

Gnomad ASJ

AF:

0.669

Gnomad EAS

AF:

0.562

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.547

Gnomad OTH

AF:

0.566

GnomAD4 exome

AF:

0.541

AC:

1733

AN:

3202

Hom.:

490

Cov.:

AF XY:

0.525

AC XY:

914

AN XY:

1742

show subpopulations

African (AFR)

AF:

0.721

AC:

AN:

136

American (AMR)

AF:

0.487

AC:

152

AN:

312

Ashkenazi Jewish (ASJ)

AF:

0.745

AC:

AN:

110

East Asian (EAS)

AF:

0.620

AC:

AN:

100

South Asian (SAS)

AF:

0.387

AC:

AN:

106

European-Finnish (FIN)

AF:

0.521

AC:

AN:

Middle Eastern (MID)

AF:

0.700

AC:

AN:

European-Non Finnish (NFE)

AF:

0.532

AC:

1145

AN:

2154

Other (OTH)

AF:

0.539

AC:

AN:

178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

120

160

200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.570

AC:

86559

AN:

151910

Hom.:

24818

Cov.:

AF XY:

0.567

AC XY:

42088

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.644

AC:

26673

AN:

41440

American (AMR)

AF:

0.516

AC:

7884

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

2319

AN:

3466

East Asian (EAS)

AF:

0.563

AC:

2885

AN:

5128

South Asian (SAS)

AF:

0.457

AC:

2195

AN:

4798

European-Finnish (FIN)

AF:

0.526

AC:

5564

AN:

10568

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.547

AC:

37174

AN:

67930

Other (OTH)

AF:

0.562

AC:

1184

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1887

3775

5662

7550

9437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<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:

0.552

Hom.:

41084

Bravo

AF:

0.574

Asia WGS

AF:

0.514

AC:

1786

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.43

(source)

DANN

Benign

0.38

PhyloP100

-0.94

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