rs778713639

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001257359.2(SAMD14):​c.1142G>T​(p.Arg381Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,230 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R381H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SAMD14
NM_001257359.2 missense

Scores

2
13
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.21
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SAMD14NM_001257359.2 linkc.1142G>T p.Arg381Leu missense_variant Exon 10 of 10 ENST00000330175.9 NP_001244288.1 Q8IZD0-1
SAMD14NM_174920.4 linkc.1226G>T p.Arg409Leu missense_variant Exon 11 of 11 NP_777580.1 Q8IZD0-2
SAMD14XM_017024322.3 linkc.1391G>T p.Arg464Leu missense_variant Exon 9 of 9 XP_016879811.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SAMD14ENST00000330175.9 linkc.1142G>T p.Arg381Leu missense_variant Exon 10 of 10 1 NM_001257359.2 ENSP00000329144.4 Q8IZD0-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152230
Hom.:
0
Cov.:
32
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152230
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74384
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.87
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;.;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.65
D;D;D
MetaSVM
Uncertain
0.53
D
MutationAssessor
Benign
2.0
M;.;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-4.7
D;D;D
REVEL
Uncertain
0.54
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.011
D;D;D
Polyphen
0.98
D;.;D
Vest4
0.47
MutPred
0.60
Loss of methylation at K384 (P = 0.0405);.;.;
MVP
0.82
MPC
0.19
ClinPred
0.98
D
GERP RS
5.1
Varity_R
0.52
gMVP
0.52

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.

Other links and lift over

dbSNP: rs778713639; hg19: chr17-48190369; API