chr14-54737254-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015589.6(SAMD4A):​c.946A>G​(p.Asn316Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

SAMD4A
NM_015589.6 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2844221).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAMD4ANM_015589.6 linkuse as main transcriptc.946A>G p.Asn316Asp missense_variant 4/13 ENST00000554335.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAMD4AENST00000554335.6 linkuse as main transcriptc.946A>G p.Asn316Asp missense_variant 4/135 NM_015589.6 A1Q9UPU9-1
SAMD4AENST00000251091.9 linkuse as main transcriptc.716-11561A>G intron_variant 1 P4Q9UPU9-3
SAMD4AENST00000392067.7 linkuse as main transcriptc.946A>G p.Asn316Asp missense_variant 3/122 A1Q9UPU9-1
SAMD4AENST00000631086.2 linkuse as main transcriptc.-248-11561A>G intron_variant 5

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
31

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 GeneticsJan 18, 2022The c.946A>G (p.N316D) alteration is located in exon 3 (coding exon 3) of the SAMD4A gene. This alteration results from a A to G substitution at nucleotide position 946, causing the asparagine (N) at amino acid position 316 to be replaced by an aspartic acid (D). 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
Uncertain
0.40
BayesDel_addAF
Benign
-0.034
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.046
T;T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
.;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.28
T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
1.7
L;L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-2.3
N;N
REVEL
Benign
0.17
Sift
Benign
0.036
D;D
Sift4G
Benign
0.14
T;T
Polyphen
0.65
P;P
Vest4
0.48
MutPred
0.21
Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP
0.28
MPC
0.84
ClinPred
0.95
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.27
gMVP
0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-55203972; API