chr14-54760287-C-T

Variant summary

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

The NM_015589.6(SAMD4A):​c.1303C>T​(p.Pro435Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SAMD4A
NM_015589.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.925
Variant links:
Genes affected
SAMD4A (HGNC:23023): (sterile alpha motif domain containing 4A) Sterile alpha motifs (SAMs) in proteins such as SAMD4A are part of an RNA-binding domain that functions as a posttranscriptional regulator by binding to an RNA sequence motif known as the Smaug recognition element, which was named after the Drosophila Smaug protein (Baez and Boccaccio, 2005 [PubMed 16221671]).[supplied by OMIM, Mar 2008]

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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=0.052315027).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SAMD4ANM_015589.6 linkc.1303C>T p.Pro435Ser missense_variant Exon 7 of 13 ENST00000554335.6 NP_056404.4 Q9UPU9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SAMD4AENST00000554335.6 linkc.1303C>T p.Pro435Ser missense_variant Exon 7 of 13 5 NM_015589.6 ENSP00000452535.1 Q9UPU9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1303C>T (p.P435S) alteration is located in exon 6 (coding exon 6) of the SAMD4A gene. This alteration results from a C to T substitution at nucleotide position 1303, causing the proline (P) at amino acid position 435 to be replaced by a serine (S). 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
0.062
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
4.7
DANN
Benign
0.96
DEOGEN2
Benign
0.0062
T;.;.;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.70
.;T;T;T;.
M_CAP
Benign
0.0057
T
MetaRNN
Benign
0.052
T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.34
N;.;.;N;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.22
N;.;.;N;N
REVEL
Benign
0.018
Sift
Benign
0.22
T;.;.;T;T
Sift4G
Benign
0.59
T;T;T;T;T
Polyphen
0.0
B;B;B;B;B
Vest4
0.11
MutPred
0.14
Gain of phosphorylation at P435 (P = 0.0062);.;.;Gain of phosphorylation at P435 (P = 0.0062);.;
MVP
0.043
MPC
0.52
ClinPred
0.043
T
GERP RS
0.13
Varity_R
0.054
gMVP
0.26

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: rs1594907536; hg19: chr14-55227005; API