Variant 17-50112910-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000330175.9(SAMD14):c.1237G>A(p.Glu413Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,606,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SAMD14
ENST00000330175.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.37

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2165255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SAMD14	NM_001257359.2 linkuse as main transcript	c.1237G>A	p.Glu413Lys	missense_variant	10/10	ENST00000330175.9	NP_001244288.1
SAMD14	NM_174920.4 linkuse as main transcript	c.1321G>A	p.Glu441Lys	missense_variant	11/11		NP_777580.1
SAMD14	XM_017024322.3 linkuse as main transcript	c.1486G>A	p.Glu496Lys	missense_variant	9/9		XP_016879811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMD14	ENST00000330175.9 linkuse as main transcript	c.1237G>A	p.Glu413Lys	missense_variant	10/10	1	NM_001257359.2	ENSP00000329144	P1	Q8IZD0-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000204

AC:

AN:

245492

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133332

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1453874

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

723668

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000436

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000284

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

The c.1321G>A (p.E441K) alteration is located in exon 11 (coding exon 10) of the SAMD14 gene. This alteration results from a G to A substitution at nucleotide position 1321, causing the glutamic acid (E) at amino acid position 441 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.087

T;.;.

Eigen

Benign

0.078

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

M;.;.

MutationTaster

Benign

0.96

N;N

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.5

N;N;N

REVEL

Benign

0.091

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.030

D;D;D

Polyphen

0.99

D;.;B

Vest4

0.30

MutPred

0.19

Gain of methylation at E413 (P = 0.0072);.;.;

MVP

0.58

MPC

0.17

ClinPred

0.71

GERP RS

4.1

Varity_R

0.24

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over