rs1957358

Variant names:

• chr14-54755757-T-C
• rs1957358
• NM_015589.6:c.1176+4220T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-54755757-T-C
• chr14-54755757-T-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015589.6(SAMD4A):​c.1176+4220T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,956 control chromosomes in the GnomAD database, including 18,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (★).

• Frequency: Genomes: 𝑓 0.47 (18060 hom., cov: 31)
• Consequence: SAMD4A NM_015589.6 intron
• Clinical Significance: association criteria provided, single submitter O:1
• Conservation: PhyloP100: -0.260
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

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.1176+4220T>C		intron	N/A	NP_056404.4	Q9UPU9-1
	SAMD4A	NM_001161576.2		c.912+4220T>C		intron	N/A	NP_001155048.2	Q9UPU9-3
	SAMD4A	NM_001161577.2		c.-52+860T>C		intron	N/A	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.1176+4220T>C		intron	N/A	ENSP00000452535.1	Q9UPU9-1
	SAMD4A	ENST00000251091.9	TSL:1	c.912+4220T>C		intron	N/A	ENSP00000251091.5	Q9UPU9-3
	SAMD4A	ENST00000555192.1	TSL:1	c.-52+860T>C		intron	N/A	ENSP00000450808.1	G3V2R1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71909 AN: 151838 Hom.: 18058 Cov.: 31

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.473 AC: 71931 AN: 151956 Hom.: 18060 Cov.: 31 AF XY: 0.465 AC XY: 34489 AN XY: 74248

African (AFR) AF: 0.344 AC: 14235 AN: 41418

American (AMR) AF: 0.386 AC: 5895 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2030 AN: 3470

East Asian (EAS) AF: 0.350 AC: 1810 AN: 5170

South Asian (SAS) AF: 0.430 AC: 2069 AN: 4812

European-Finnish (FIN) AF: 0.474 AC: 5001 AN: 10554

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39104 AN: 67946

Other (OTH) AF: 0.482 AC: 1014 AN: 2104

Alfa AF: 0.549 Hom.: 46644

Bravo AF: 0.459

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

ClinVar submissions

Significance: association

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	-	Lip and oral cavity carcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.56
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs1957358; hg19: chr14-55222475;