Variant 14-54764449-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015589.6(SAMD4A):c.1511-6T>C variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.1128

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.474

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 id is 778740.Status of the report is criteria_provided_single_submitter, 1 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1909 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMD4A	NM_015589.6 linkuse as main transcript	c.1511-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000554335.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMD4A	ENST00000554335.6 linkuse as main transcript	c.1511-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_015589.6	A1	Q9UPU9-1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1910

AN:

152200

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00315

AC:

743

AN:

235740

Hom.:

AF XY:

0.00233

AC XY:

297

AN XY:

127218

show subpopulations

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 SAS exome

AF:

0.0000763

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.:

Cov.:

AF XY:

0.00110

AC XY:

783

AN XY:

712912

show subpopulations

Gnomad4 AFR exome

AF:

0.0446

Gnomad4 AMR exome

AF:

0.00270

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000584

Gnomad4 OTH exome

AF:

0.00304

GnomAD4 genome

AF:

0.0125

AC:

1909

AN:

152318

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

918

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0433

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00536

Hom.:

Bravo

AF:

0.0148

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.7

DANN

Benign

0.85

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over