Variant chr14-34996578-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003136.4(SRP54):c.-33-99T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 675,730 control chromosomes in the GnomAD database, including 15,106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2760 hom., cov: 32)

Exomes 𝑓: 0.21 ( 12346 hom. )

Consequence

SRP54
NM_003136.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.324

Variant links:

Genes affected

SRP54 (HGNC:11301): (signal recognition particle 54) Enables several functions, including 7S RNA binding activity; endoplasmic reticulum signal peptide binding activity; and guanyl ribonucleotide binding activity. Contributes to GTPase activity. Involved in granulocyte differentiation and protein targeting to ER. Located in cytosol and nucleus. Part of signal recognition particle, endoplasmic reticulum targeting. Implicated in severe congenital neutropenia 8. [provided by Alliance of Genome Resources, Apr 2022]

SRP54 links:

SRP54 (HGNC:):

SRP54 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 14-34996578-T-A is Benign according to our data. Variant chr14-34996578-T-A is described in ClinVar as [Benign]. Clinvar id is 1231936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SRP54	NM_003136.4 linkuse as main transcript	c.-33-99T>A	intron_variant	ENST00000216774.11	NP_003127.1	P61011-1
SRP54	NM_001146282.2 linkuse as main transcript	c.-88-99T>A	intron_variant		NP_001139754.1	P61011-2
SRP54	NM_001411017.1 linkuse as main transcript	c.-33-99T>A	intron_variant		NP_001397946.1
SRP54	XM_011537106.1 linkuse as main transcript	c.-33-99T>A	intron_variant		XP_011535408.1	P61011-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRP54	ENST00000216774.11 linkuse as main transcript	c.-33-99T>A		intron_variant		1	NM_003136.4	ENSP00000216774.6		P61011-1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26298

AN:

152026

Hom.:

2755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0656

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.191

GnomAD4 exome

AF:

0.207

AC:

108309

AN:

523586

Hom.:

12346

AF XY:

0.207

AC XY:

58321

AN XY:

281234

show subpopulations

Gnomad4 AFR exome

AF:

0.0632

Gnomad4 AMR exome

AF:

0.216

Gnomad4 ASJ exome

AF:

0.264

Gnomad4 EAS exome

AF:

0.386

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.222

Gnomad4 NFE exome

AF:

0.185

Gnomad4 OTH exome

AF:

0.205

GnomAD4 genome

AF:

0.173

AC:

26314

AN:

152144

Hom.:

2760

Cov.:

AF XY:

0.178

AC XY:

13274

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0656

Gnomad4 AMR

AF:

0.235

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.382

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.196

Alfa

AF:

0.175

Hom.:

315

Bravo

AF:

0.167

Asia WGS

AF:

0.308

AC:

1066

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.0

DANN

Benign

0.77

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

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