Genetic Variant SAMD4A:p.Pro463Leu (chr14-54760372-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015589.6(SAMD4A):c.1388C>T(p.Pro463Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SAMD4A
NM_015589.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34

Publications

0 publications found

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]

SAMD4A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08891812).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015589.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD4A	NM_015589.6	MANE Select	c.1388C>T	p.Pro463Leu	missense	Exon 7 of 13	NP_056404.4	Q9UPU9-1
SAMD4A	NM_001161576.2		c.1124C>T	p.Pro375Leu	missense	Exon 5 of 11	NP_001155048.2	Q9UPU9-3
SAMD4A	NM_001161577.2		c.161C>T	p.Pro54Leu	missense	Exon 2 of 9	NP_001155049.1	G3V2R1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD4A	ENST00000554335.6	TSL:5 MANE Select	c.1388C>T	p.Pro463Leu	missense	Exon 7 of 13	ENSP00000452535.1	Q9UPU9-1
SAMD4A	ENST00000251091.9	TSL:1	c.1124C>T	p.Pro375Leu	missense	Exon 5 of 11	ENSP00000251091.5	Q9UPU9-3
SAMD4A	ENST00000555192.1	TSL:1	c.161C>T	p.Pro54Leu	missense	Exon 2 of 9	ENSP00000450808.1	G3V2R1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

164582

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1403014

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696200

African (AFR)

AF:

0.00

AC:

AN:

29918

American (AMR)

AF:

0.00

AC:

AN:

34010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24180

East Asian (EAS)

AF:

0.00

AC:

AN:

36814

South Asian (SAS)

AF:

0.00

AC:

AN:

80602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091970

Other (OTH)

AF:

0.00

AC:

AN:

58138

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.23

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.012

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

1.3

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.1

REVEL

Benign

0.047

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.049

Polyphen

0.0

Vest4

0.15

MutPred

0.27

Loss of glycosylation at P463 (P = 0.0453)

MVP

0.043

MPC

0.53

ClinPred

0.24

GERP RS

4.4

Varity_R

0.065

gMVP

0.13

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over