rs1053271797

Variant names:

• chr14-54760372-C-A
• rs1053271797
• NM_015589.6:c.1388C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-54760372-C-A
• chr14-54760372-C-G
• chr14-54760372-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015589.6(SAMD4A):​c.1388C>A​(p.Pro463His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,403,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P463L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SAMD4A NM_015589.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09711254).

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.1388C>A	p.Pro463His	missense	Exon 7 of 13	NP_056404.4	Q9UPU9-1
	SAMD4A	NM_001161576.2		c.1124C>A	p.Pro375His	missense	Exon 5 of 11	NP_001155048.2	Q9UPU9-3
	SAMD4A	NM_001161577.2		c.161C>A	p.Pro54His	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.1388C>A	p.Pro463His	missense	Exon 7 of 13	ENSP00000452535.1	Q9UPU9-1
	SAMD4A	ENST00000251091.9	TSL:1	c.1124C>A	p.Pro375His	missense	Exon 5 of 11	ENSP00000251091.5	Q9UPU9-3
	SAMD4A	ENST00000555192.1	TSL:1	c.161C>A	p.Pro54His	missense	Exon 2 of 9	ENSP00000450808.1	G3V2R1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1403012 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 696198

African (AFR) AF: 0.00 AC: 0 AN: 29918

American (AMR) AF: 0.00 AC: 0 AN: 34010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24180

East Asian (EAS) AF: 0.00 AC: 0 AN: 36814

South Asian (SAS) AF: 0.00 AC: 0 AN: 80602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 9.16e-7 AC: 1 AN: 1091968

Other (OTH) AF: 0.00 AC: 0 AN: 58138

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		1.3
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.12
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.12	B
Vest4		0.15
MutPred		0.25		Gain of catalytic residue at P463 (P = 0.0373)
MVP		0.043
MPC		0.63
ClinPred		0.33	T
GERP RS		4.4
Varity_R		0.091
gMVP		0.14
Mutation Taster		=92/8	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: rs1053271797; hg19: chr14-55227090;