rs139601106

Variant names:

• chr14-54774964-G-A
• rs139601106
• NM_015589.6:c.1746G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_015589.6(SAMD4A):​c.1746G>A​(p.Pro582Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000967 in 1,614,160 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (2 hom.)
• Consequence: SAMD4A NM_015589.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.456
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 14-54774964-G-A is Benign according to our data. Variant chr14-54774964-G-A is described in ClinVar as Benign. ClinVar VariationId is 716181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.456 with no splicing effect.
• BS2: High AC in GnomAd4 at 453 AD gene.

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.1746G>A	p.Pro582Pro	synonymous	Exon 10 of 13	NP_056404.4	Q9UPU9-1
	SAMD4A	NM_001161576.2		c.1482G>A	p.Pro494Pro	synonymous	Exon 8 of 11	NP_001155048.2	Q9UPU9-3
	SAMD4A	NM_001161577.2		c.519G>A	p.Pro173Pro	synonymous	Exon 5 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.1746G>A	p.Pro582Pro	synonymous	Exon 10 of 13	ENSP00000452535.1	Q9UPU9-1
	SAMD4A	ENST00000251091.9	TSL:1	c.1482G>A	p.Pro494Pro	synonymous	Exon 8 of 11	ENSP00000251091.5	Q9UPU9-3
	SAMD4A	ENST00000555192.1	TSL:1	c.519G>A	p.Pro173Pro	synonymous	Exon 5 of 9	ENSP00000450808.1	G3V2R1

Frequencies

GnomAD3 genomes AF: 0.00296 AC: 451 AN: 152154 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00939

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000927 AC: 233 AN: 251300 AF XY: 0.000655

Gnomad AFR exome AF: 0.00997

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000502

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000758 AC: 1108 AN: 1461888 Hom.: 2 Cov.: 33 AF XY: 0.000704 AC XY: 512 AN XY: 727246

African (AFR) AF: 0.00992 AC: 332 AN: 33480

American (AMR) AF: 0.000380 AC: 17 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53418

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000629 AC: 700 AN: 1112008

Other (OTH) AF: 0.000861 AC: 52 AN: 60396

GnomAD4 genome AF: 0.00297 AC: 453 AN: 152272 Hom.: 1 Cov.: 32 AF XY: 0.00266 AC XY: 198 AN XY: 74458

African (AFR) AF: 0.00941 AC: 391 AN: 41560

American (AMR) AF: 0.00150 AC: 23 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000514 AC: 35 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00180 Hom.: 0

Bravo AF: 0.00385

EpiCase AF: 0.000709

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.0
DANN	Benign	0.64
PhyloP100		-0.46
Mutation Taster		=97/3	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: rs139601106; hg19: chr14-55241682; COSMIC: COSV51882002; COSMIC: COSV51882002;