rs1594907536

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-54760287-C-G
• chr14-54760287-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015589.6(SAMD4A):​c.1303C>G​(p.Pro435Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P435S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SAMD4A NM_015589.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.925

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059878886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD4A	NM_015589.6	c.1303C>G	p.Pro435Ala	missense_variant	Exon 7 of 13	ENST00000554335.6	NP_056404.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD4A	ENST00000554335.6	c.1303C>G	p.Pro435Ala	missense_variant	Exon 7 of 13	5	NM_015589.6	ENSP00000452535.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459664 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726196

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.5
DANN	Benign	0.92
DEOGEN2	Benign	0.0066	T;.;.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.72	.;T;T;T;.
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.060	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.;.;N;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.44	N;.;.;N;N
REVEL	Benign	0.018
Sift	Benign	0.48	T;.;.;T;T
Sift4G	Benign	0.49	T;T;T;T;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.18
MutPred		0.16		Loss of glycosylation at P435 (P = 0.0255);.;.;Loss of glycosylation at P435 (P = 0.0255);.;
MVP		0.068
MPC		0.50
ClinPred		0.025	T
GERP RS		0.13
Varity_R		0.049
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs1594907536; hg19: chr14-55227005;