rs1594907536

Variant summary

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

The NM_015589.6(SAMD4A):​c.1303C>G​(p.Pro435Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,664 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. 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. P435S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

SAMD4A
NM_015589.6 missense

Scores

19

Clinical Significance

Not reported in ClinVar

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]

Genome browser will be placed here

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=0.059878886).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SAMD4ANM_015589.6 linkc.1303C>G p.Pro435Ala 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>G p.Pro435Ala missense_variant Exon 7 of 13 5 NM_015589.6 ENSP00000452535.1 Q9UPU9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459664
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726196
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.053
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
5.5
DANN
Benign
0.92
DEOGEN2
Benign
0.0066
T;.;.;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.35
N
LIST_S2
Benign
0.72
.;T;T;T;.
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.060
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;.;.;N;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.44
N;.;.;N;N
REVEL
Benign
0.018
Sift
Benign
0.48
T;.;.;T;T
Sift4G
Benign
0.49
T;T;T;T;T
Polyphen
0.0
B;B;B;B;B
Vest4
0.18
MutPred
0.16
Loss of glycosylation at P435 (P = 0.0255);.;.;Loss of glycosylation at P435 (P = 0.0255);.;
MVP
0.068
MPC
0.50
ClinPred
0.025
T
GERP RS
0.13
Varity_R
0.049
gMVP
0.22

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