Variant chr14-54568111-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015589.6(SAMD4A):c.195C>T(p.Pro65=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000998 in 1,513,208 control chromosomes in the GnomAD database, including 16 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 0.0052 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 5 hom. )

Consequence

SAMD4A
NM_015589.6 splice_region, synonymous

Scores

Splicing: ADA: 0.00007261

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.35

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 14-54568111-C-T is Benign according to our data. Variant chr14-54568111-C-T is described in ClinVar as [Benign]. Clinvar id is 711102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-54568111-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.35 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00524 (798/152198) while in subpopulation AFR AF= 0.0181 (753/41514). AF 95% confidence interval is 0.0171. There are 11 homozygotes in gnomad4. There are 387 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 798 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMD4A	NM_015589.6 linkuse as main transcript	c.195C>T	p.Pro65=	splice_region_variant, synonymous_variant	2/13	ENST00000554335.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMD4A	ENST00000554335.6 linkuse as main transcript	c.195C>T	p.Pro65=	splice_region_variant, synonymous_variant	2/13	5	NM_015589.6	A1	Q9UPU9-1

Frequencies

GnomAD3 genomes

AF:

0.00521

AC:

793

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00109

AC:

137

AN:

125946

Hom.:

AF XY:

0.000883

AC XY:

AN XY:

70220

show subpopulations

Gnomad AFR exome

AF:

0.0254

Gnomad AMR exome

AF:

0.000761

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000878

Gnomad OTH exome

AF:

0.000852

GnomAD4 exome

AF:

0.000523

AC:

712

AN:

1361010

Hom.:

Cov.:

AF XY:

0.000450

AC XY:

302

AN XY:

670738

show subpopulations

Gnomad4 AFR exome

AF:

0.0188

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000647

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000551

Gnomad4 OTH exome

AF:

0.00127

GnomAD4 genome

AF:

0.00524

AC:

798

AN:

152198

Hom.:

Cov.:

AF XY:

0.00520

AC XY:

387

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0181

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.00603

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

-0.57

CADD

Benign

1.9

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000073

dbscSNV1_RF

Benign

0.11

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

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