14-54737234-A-T

Position:

• chr14-54737234-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015589.6(SAMD4A):​c.926A>T​(p.Glu309Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SAMD4A NM_015589.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAMD4A	NM_015589.6	c.926A>T	p.Glu309Val	missense_variant	4/13	ENST00000554335.6	NP_056404.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMD4A	ENST00000554335.6	c.926A>T	p.Glu309Val	missense_variant	4/13	5	NM_015589.6	ENSP00000452535.1
SAMD4A	ENST00000251091.9	c.716-11581A>T		intron_variant		1		ENSP00000251091.5
SAMD4A	ENST00000392067.7	c.926A>T	p.Glu309Val	missense_variant	3/12	2		ENSP00000375919.3
SAMD4A	ENST00000631086.2	c.-248-11581A>T		intron_variant		5		ENSP00000486821.1

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.926A>T (p.E309V) alteration is located in exon 3 (coding exon 3) of the SAMD4A gene. This alteration results from a A to T substitution at nucleotide position 926, causing the glutamic acid (E) at amino acid position 309 to be replaced by a valine (V). 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	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.036	D;D
Polyphen		0.97	D;D
Vest4		0.67
MutPred		0.23		Loss of solvent accessibility (P = 0.0199);Loss of solvent accessibility (P = 0.0199);
MVP		0.22
MPC		1.3
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.45

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: chr14-55203952;