14-54751453-T-A

Position:

• chr14-54751453-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015589.6(SAMD4A):​c.1092T>A​(p.Asn364Lys) variant causes a missense, splice region 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SAMD4A NM_015589.6 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.642

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082749814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMD4A	NM_015589.6	c.1092T>A	p.Asn364Lys	missense_variant, splice_region_variant	6/13	ENST00000554335.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMD4A	ENST00000554335.6	c.1092T>A	p.Asn364Lys	missense_variant, splice_region_variant	6/13	5	NM_015589.6	A1
SAMD4A	ENST00000251091.9	c.828T>A	p.Asn276Lys	missense_variant, splice_region_variant	4/11	1		P4
SAMD4A	ENST00000392067.7	c.1092T>A	p.Asn364Lys	missense_variant, splice_region_variant	5/12	2		A1
SAMD4A	ENST00000631086.2	c.-136T>A		splice_region_variant, 5_prime_UTR_variant	4/12	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

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

Mar 07, 2024

The c.1092T>A (p.N364K) alteration is located in exon 5 (coding exon 5) of the SAMD4A gene. This alteration results from a T to A substitution at nucleotide position 1092, causing the asparagine (N) at amino acid position 364 to be replaced by a lysine (K). 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	0.57
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T;.;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.16	N
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.083	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L;.;L
MutationTaster	Benign	0.99	D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.4	D;.;D
REVEL	Benign	0.19
Sift	Benign	0.062	T;.;T
Sift4G	Benign	0.39	T;T;T
Polyphen		0.051	B;B;B
Vest4		0.31
MutPred		0.58		Gain of MoRF binding (P = 0.0448);.;Gain of MoRF binding (P = 0.0448);
MVP		0.068
MPC		0.70
ClinPred		0.82	D
GERP RS		-4.6
Varity_R		0.48
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr14-55218171;