rs17657012

Positions:

• chr14-54709626-A-G

Variant summary

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

The NM_015589.6(SAMD4A):​c.715+7046A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 152,150 control chromosomes in the GnomAD database, including 369 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 0.060 (369 hom., cov: 32)
• Consequence: SAMD4A NM_015589.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141

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]

SAMD4A-AS1 (HGNC:54803): (SAMD4A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMD4A	NM_015589.6	c.715+7046A>G		intron_variant		ENST00000554335.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMD4A	ENST00000554335.6	c.715+7046A>G		intron_variant		5	NM_015589.6	A1
SAMD4A-AS1	ENST00000691091.2	n.428+19271T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0596 AC: 9058 AN: 152034 Hom.: 368 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0438

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0842

Gnomad OTH AF: 0.0532

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

GnomAD4 genome AF: 0.0596 AC: 9072 AN: 152150 Hom.: 369 Cov.: 32 AF XY: 0.0609 AC XY: 4532 AN XY: 74372

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.0438

Gnomad4 ASJ AF: 0.0591

Gnomad4 EAS AF: 0.0193

Gnomad4 SAS AF: 0.0656

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0842

Gnomad4 OTH AF: 0.0517

Alfa AF: 0.0780 Hom.: 198

Bravo AF: 0.0516

Asia WGS AF: 0.0390 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.73
DANN	Benign	0.41

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: rs17657012; hg19: chr14-55176344;