Variant chr14-35028060-C-T 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.1328-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,521,576 control chromosomes in the GnomAD database, including 9,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 601 hom., cov: 31)

Exomes 𝑓: 0.11 ( 9134 hom. )

Consequence

SRP54
NM_003136.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.477

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 14-35028060-C-T is Benign according to our data. Variant chr14-35028060-C-T is described in ClinVar as [Benign]. Clinvar id is 1221356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRP54	NM_003136.4 linkuse as main transcript	c.1328-28C>T		intron_variant		ENST00000216774.11	NP_003127.1	P61011-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRP54	ENST00000216774.11 linkuse as main transcript	c.1328-28C>T		intron_variant		1	NM_003136.4	ENSP00000216774.6		P61011-1

Frequencies

GnomAD3 genomes

AF:

0.0773

AC:

11732

AN:

151840

Hom.:

602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0195

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0678

Gnomad ASJ

AF:

0.0692

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0968

Gnomad FIN

AF:

0.0551

Gnomad MID

AF:

0.0962

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.0744

GnomAD3 exomes

AF:

0.0853

AC:

20498

AN:

240276

Hom.:

1101

AF XY:

0.0903

AC XY:

11762

AN XY:

130206

show subpopulations

Gnomad AFR exome

AF:

0.0197

Gnomad AMR exome

AF:

0.0530

Gnomad ASJ exome

AF:

0.0669

Gnomad EAS exome

AF:

0.000511

Gnomad SAS exome

AF:

0.0990

Gnomad FIN exome

AF:

0.0593

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.0986

GnomAD4 exome

AF:

0.109

AC:

148670

AN:

1369618

Hom.:

9134

Cov.:

AF XY:

0.109

AC XY:

74673

AN XY:

685858

show subpopulations

Gnomad4 AFR exome

AF:

0.0176

Gnomad4 AMR exome

AF:

0.0538

Gnomad4 ASJ exome

AF:

0.0676

Gnomad4 EAS exome

AF:

0.000331

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.0638

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.0974

GnomAD4 genome

AF:

0.0772

AC:

11727

AN:

151958

Hom.:

601

Cov.:

AF XY:

0.0742

AC XY:

5506

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.0194

Gnomad4 AMR

AF:

0.0677

Gnomad4 ASJ

AF:

0.0692

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0969

Gnomad4 FIN

AF:

0.0551

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.0731

Alfa

AF:

0.116

Hom.:

1442

Bravo

AF:

0.0746

Asia WGS

AF:

0.0380

AC:

135

AN:

3478

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 15, 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

-0.84

CADD

Benign

0.23

DANN

Benign

0.55

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