chr14-54760287-C-T

Variant names:

• chr14-54760287-C-T
• rs1594907536
• NM_015589.6:c.1303C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015589.6(SAMD4A):​c.1303C>T​(p.Pro435Ser) 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. 16/21 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)
• Consequence: SAMD4A NM_015589.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.925
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052315027).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD4A	NM_015589.6	MANE Select	c.1303C>T	p.Pro435Ser	missense	Exon 7 of 13	NP_056404.4	Q9UPU9-1
	SAMD4A	NM_001161576.2		c.1039C>T	p.Pro347Ser	missense	Exon 5 of 11	NP_001155048.2	Q9UPU9-3
	SAMD4A	NM_001161577.2		c.76C>T	p.Pro26Ser	missense	Exon 2 of 9	NP_001155049.1	G3V2R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD4A	ENST00000554335.6	TSL:5 MANE Select	c.1303C>T	p.Pro435Ser	missense	Exon 7 of 13	ENSP00000452535.1	Q9UPU9-1
	SAMD4A	ENST00000251091.9	TSL:1	c.1039C>T	p.Pro347Ser	missense	Exon 5 of 11	ENSP00000251091.5	Q9UPU9-3
	SAMD4A	ENST00000555192.1	TSL:1	c.76C>T	p.Pro26Ser	missense	Exon 2 of 9	ENSP00000450808.1	G3V2R1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.7
DANN	Benign	0.96
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.93
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.018
Sift	Benign	0.22	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.14		Gain of phosphorylation at P435 (P = 0.0062)
MVP		0.043
MPC		0.52
ClinPred		0.043	T
GERP RS		0.13
Varity_R		0.054
gMVP		0.26
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1594907536; hg19: chr14-55227005;