17-50113973-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001257359.2(SAMD14):​c.1049G>A​(p.Arg350Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000868 in 1,613,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

SAMD14
NM_001257359.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.870
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03902477).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SAMD14NM_001257359.2 linkc.1049G>A p.Arg350Gln missense_variant Exon 9 of 10 ENST00000330175.9 NP_001244288.1 Q8IZD0-1
SAMD14NM_174920.4 linkc.1133G>A p.Arg378Gln missense_variant Exon 10 of 11 NP_777580.1 Q8IZD0-2
SAMD14XM_017024322.3 linkc.1298G>A p.Arg433Gln missense_variant Exon 8 of 9 XP_016879811.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SAMD14ENST00000330175.9 linkc.1049G>A p.Arg350Gln missense_variant Exon 9 of 10 1 NM_001257359.2 ENSP00000329144.4 Q8IZD0-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152206
Hom.:
0
Cov.:
32
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000677
AC:
17
AN:
251232
Hom.:
0
AF XY:
0.0000736
AC XY:
10
AN XY:
135854
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000931
AC:
136
AN:
1461432
Hom.:
0
Cov.:
31
AF XY:
0.0000825
AC XY:
60
AN XY:
727044
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000105
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152324
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.0000653
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:
0.0000231
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1133G>A (p.R378Q) alteration is located in exon 10 (coding exon 9) of the SAMD14 gene. This alteration results from a G to A substitution at nucleotide position 1133, causing the arginine (R) at amino acid position 378 to be replaced by a glutamine (Q). 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
Benign
0.071
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
18
DANN
Benign
0.59
DEOGEN2
Benign
0.027
T;.;.
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.28
FATHMM_MKL
Benign
0.11
N
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.054
D
MetaRNN
Benign
0.039
T;T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
-0.18
N;.;.
PrimateAI
Benign
0.32
T
PROVEAN
Benign
0.19
N;N;N
REVEL
Benign
0.24
Sift
Benign
1.0
T;T;T
Sift4G
Benign
0.43
T;T;T
Polyphen
0.81
P;.;P
Vest4
0.10
MVP
0.78
MPC
0.20
ClinPred
0.082
T
GERP RS
4.8
Varity_R
0.065
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs564137587; hg19: chr17-48191337; COSMIC: COSV50303523; COSMIC: COSV50303523; API