Variant 19-39370008-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001384574.2(SAMD4B):c.550G>A(p.Gly184Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.0000021 ( 0 hom. )

Consequence

SAMD4B
NM_001384574.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

Variant links:

Genes affected

SAMD4B (HGNC:25492): (sterile alpha motif domain containing 4B) Enables RNA binding activity. Predicted to be involved in nuclear-transcribed mRNA poly(A) tail shortening. Predicted to act upstream of or within cerebellar neuron development. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

SAMD4B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10750428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMD4B	NM_001384574.2 linkuse as main transcript	c.550G>A	p.Gly184Arg	missense_variant	4/14	ENST00000610417.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMD4B	ENST00000610417.5 linkuse as main transcript	c.550G>A	p.Gly184Arg	missense_variant	4/14	2	NM_001384574.2	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

245530

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133506

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:

0.0000271

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460634

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726584

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.550G>A (p.G184R) alteration is located in exon 6 (coding exon 2) of the SAMD4B gene. This alteration results from a G to A substitution at nucleotide position 550, causing the glycine (G) at amino acid position 184 to be replaced by an arginine (R). 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

0.23

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;T;.;T;T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.085

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

T;.;D;T;T;D

M_CAP

Benign

0.0036

MetaRNN

Benign

0.11

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

.;L;.;L;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.3

.;N;.;.;.;.

REVEL

Benign

0.016

Sift

Benign

0.079

.;T;.;.;.;.

Sift4G

Benign

0.30

T;T;T;T;T;T

Polyphen

0.016

.;B;.;B;.;.

Vest4

0.35

MutPred

0.22

Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);

MVP

0.043

MPC

1.3

ClinPred

0.12

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.054

gMVP

0.41

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over