14-54760252-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015589.6(SAMD4A):​c.1268C>G​(p.Thr423Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,852 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SAMD4A
NM_015589.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.00
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.047583997).
BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SAMD4ANM_015589.6 linkc.1268C>G p.Thr423Ser 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.1268C>G p.Thr423Ser missense_variant Exon 7 of 13 5 NM_015589.6 ENSP00000452535.1 Q9UPU9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1460852
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
726748
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
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
Oct 10, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1268C>G (p.T423S) alteration is located in exon 6 (coding exon 6) of the SAMD4A gene. This alteration results from a C to G substitution at nucleotide position 1268, causing the threonine (T) at amino acid position 423 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
0.066
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
10
DANN
Benign
0.48
DEOGEN2
Benign
0.0079
T;.;.;T;.
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.57
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.66
.;T;T;T;.
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.048
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-1.9
N;.;.;N;.
PrimateAI
Benign
0.47
T
PROVEAN
Benign
0.050
N;N;.;N;N
REVEL
Benign
0.11
Sift
Benign
0.41
T;T;.;T;T
Sift4G
Benign
1.0
T;T;T;T;T
Polyphen
0.0
B;B;B;B;B
Vest4
0.11
MutPred
0.16
Gain of glycosylation at T423 (P = 0.0635);.;.;Gain of glycosylation at T423 (P = 0.0635);.;
MVP
0.043
MPC
0.46
ClinPred
0.15
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.049
gMVP
0.21

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: rs2038357312; hg19: chr14-55226970; API