rs11627203

Positions:

• chr14-54754825-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+3288T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 986,312 control chromosomes in the GnomAD database, including 132,179 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 0.38 (13261 hom., cov: 32)
  • Exomes 𝑓: 0.53 (118918 hom.)
• Consequence: SAMD4A NM_015589.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145

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 = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAMD4A	NM_015589.6	c.1176+3288T>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+3288T>C		intron_variant		5	NM_015589.6	ENSP00000452535.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57414 AN: 151996 Hom.: 13260 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.528 AC: 440696 AN: 834196 Hom.: 118918 Cov.: 29 AF XY: 0.529 AC XY: 203799 AN XY: 385412

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.365

Gnomad4 FIN exome AF: 0.461

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.476

GnomAD4 genome AF: 0.377 AC: 57419 AN: 152116 Hom.: 13261 Cov.: 32 AF XY: 0.371 AC XY: 27561 AN XY: 74346

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.395

Alfa AF: 0.504 Hom.: 32249

Bravo AF: 0.355

Asia WGS AF: 0.260 AC: 901 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	2.9
DANN	Benign	0.68

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: rs11627203; hg19: chr14-55221543; COSMIC: COSV51880669; COSMIC: COSV51880669;