14-54764449-T-C

Variant names:

• chr14-54764449-T-C
• rs75839195
• NM_015589.6:c.1511-6T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015589.6(SAMD4A):​c.1511-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,584,078 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (45 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (35 hom.)
• Consequence: SAMD4A NM_015589.6 splice_region, intron
• Scores: Splicing: ADA: 0.1128
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.474
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 14-54764449-T-C is Benign according to our data. Variant chr14-54764449-T-C is described in ClinVar as Benign. ClinVar VariationId is 778740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0125 (1909/152318) while in subpopulation AFR AF = 0.0433 (1799/41574). AF 95% confidence interval is 0.0416. There are 45 homozygotes in GnomAd4. There are 918 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1909 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.1511-6T>C		splice_region intron	N/A	NP_056404.4	Q9UPU9-1
	SAMD4A	NM_001161576.2		c.1247-6T>C		splice_region intron	N/A	NP_001155048.2	Q9UPU9-3
	SAMD4A	NM_001161577.2		c.284-6T>C		splice_region 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.1511-6T>C		splice_region intron	N/A	ENSP00000452535.1	Q9UPU9-1
	SAMD4A	ENST00000251091.9	TSL:1	c.1247-6T>C		splice_region intron	N/A	ENSP00000251091.5	Q9UPU9-3
	SAMD4A	ENST00000555192.1	TSL:1	c.284-6T>C		splice_region intron	N/A	ENSP00000450808.1	G3V2R1

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1910 AN: 152200 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00315 AC: 743 AN: 235740 AF XY: 0.00233

Gnomad AFR exome AF: 0.0406

Gnomad AMR exome AF: 0.00225

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000912

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00126 AC: 1808 AN: 1431760 Hom.: 35 Cov.: 27 AF XY: 0.00110 AC XY: 783 AN XY: 712912

African (AFR) AF: 0.0446 AC: 1423 AN: 31878

American (AMR) AF: 0.00270 AC: 108 AN: 40002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25310

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.000122 AC: 10 AN: 81874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53228

Middle Eastern (MID) AF: 0.00408 AC: 23 AN: 5644

European-Non Finnish (NFE) AF: 0.0000584 AC: 64 AN: 1095102

Other (OTH) AF: 0.00304 AC: 180 AN: 59174

GnomAD4 genome AF: 0.0125 AC: 1909 AN: 152318 Hom.: 45 Cov.: 32 AF XY: 0.0123 AC XY: 918 AN XY: 74474

African (AFR) AF: 0.0433 AC: 1799 AN: 41574

American (AMR) AF: 0.00516 AC: 79 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68034

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.00531 Hom.: 13

Bravo AF: 0.0148

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.0000593

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	-0.62
CADD	Benign	5.7
DANN	Benign	0.85
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.11
dbscSNV1_RF	Benign	0.45
SpliceAI score (max)		0.020		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: rs75839195; hg19: chr14-55231167;