chr14-54760243-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_015589.6(SAMD4A):​c.1259C>T​(p.Ser420Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,992 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: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SAMD4A
NM_015589.6 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.61
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 Uncertain_significance. Variant got 2 ACMG points.

PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity SMAG1_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21617076).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAMD4ANM_015589.6 linkuse as main transcriptc.1259C>T p.Ser420Phe missense_variant 7/13 ENST00000554335.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAMD4AENST00000554335.6 linkuse as main transcriptc.1259C>T p.Ser420Phe missense_variant 7/135 NM_015589.6 A1Q9UPU9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000414
AC:
1
AN:
241668
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
132140
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000939
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460992
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726806
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 17, 2023The c.1259C>T (p.S420F) 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 1259, causing the serine (S) at amino acid position 420 to be replaced by a phenylalanine (F). 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
0.10
BayesDel_addAF
Uncertain
0.018
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.034
T;.;.;T;.
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
.;D;D;D;.
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.22
T;T;T;T;T
MetaSVM
Benign
-0.58
T
MutationAssessor
Benign
1.8
L;.;.;L;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.3
N;.;.;N;N
REVEL
Benign
0.062
Sift
Uncertain
0.027
D;.;.;D;D
Sift4G
Uncertain
0.039
D;T;D;D;D
Polyphen
0.61
P;D;D;P;D
Vest4
0.44
MutPred
0.25
Loss of phosphorylation at S420 (P = 0.0143);.;.;Loss of phosphorylation at S420 (P = 0.0143);.;
MVP
0.12
MPC
0.78
ClinPred
0.44
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.10
gMVP
0.27

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: rs1334198363; hg19: chr14-55226961; API