rs17510813

chr14-35028060-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.477

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
SRP54	NM_003136.4	c.1328-28C>T		intron_variant		ENST00000216774.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRP54	ENST00000216774.11	c.1328-28C>T		intron_variant		1	NM_003136.4	P1

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11732 AN: 151840 Hom.: 602 Cov.: 31

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

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.: 19 AF XY: 0.109 AC XY: 74673 AN XY: 685858

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.: 31 AF XY: 0.0742 AC XY: 5506 AN XY: 74246

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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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

Other links and lift over

dbSNP: rs17510813; hg19: chr14-35497266;