chr14-54760222-C-T

Position:

• chr14-54760222-C-T

Variant summary

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

The NM_015589.6(SAMD4A):​c.1238C>T​(p.Thr413Ile) 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: 32)
• Consequence: SAMD4A NM_015589.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.34

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	UniProt
SAMD4A	NM_015589.6	c.1238C>T	p.Thr413Ile	missense_variant	7/13	ENST00000554335.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMD4A	ENST00000554335.6	c.1238C>T	p.Thr413Ile	missense_variant	7/13	5	NM_015589.6	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Nov 17, 2022

The c.1238C>T (p.T413I) alteration is located in exon 6 (coding exon 6) of the SAMD4A gene. This alteration results from a C to T substitution at nucleotide position 1238, causing the threonine (T) at amino acid position 413 to be replaced by an isoleucine (I). 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	0.99
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.58	D;.;.;D;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.74	D;D;D;D;D
MetaSVM	Uncertain	-0.062	T
MutationAssessor	Uncertain	2.6	M;.;.;M;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-4.2	D;.;.;D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0010	D;.;.;D;D
Sift4G	Uncertain	0.011	D;D;D;D;D
Polyphen		0.98	D;D;D;D;D
Vest4		0.99
MutPred		0.19		Loss of phosphorylation at T413 (P = 0.0787);.;.;Loss of phosphorylation at T413 (P = 0.0787);.;
MVP		0.56
MPC		0.74
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.54
gMVP		0.84

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: chr14-55226940;