rs1957356

Positions:

• chr14-54752276-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015589.6(SAMD4A):​c.1176+739T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,190 control chromosomes in the GnomAD database, including 45,480 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (45480 hom., cov: 33)
• Consequence: SAMD4A NM_015589.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.698

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAMD4A	NM_015589.6	c.1176+739T>C		intron_variant		ENST00000554335.6	NP_056404.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMD4A	ENST00000554335.6	c.1176+739T>C		intron_variant		5	NM_015589.6	ENSP00000452535.1
SAMD4A	ENST00000251091.9	c.912+739T>C		intron_variant		1		ENSP00000251091.5
SAMD4A	ENST00000392067.7	c.1176+739T>C		intron_variant		2		ENSP00000375919.3
SAMD4A	ENST00000631086.2	c.-52+739T>C		intron_variant		5		ENSP00000486821.1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117501 AN: 152072 Hom.: 45436 Cov.: 33

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.759

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.773 AC: 117598 AN: 152190 Hom.: 45480 Cov.: 33 AF XY: 0.770 AC XY: 57323 AN XY: 74410

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.786

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.757

Alfa AF: 0.782 Hom.: 61245

Bravo AF: 0.770

Asia WGS AF: 0.702 AC: 2441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.76

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: rs1957356; hg19: chr14-55218994;