14-34996578-T-A

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.-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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.324

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=-0.81).
• 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRP54	NM_003136.4	c.-33-99T>A		intron_variant		ENST00000216774.11
SRP54	NM_001146282.2	c.-88-99T>A		intron_variant
SRP54	NM_001411017.1	c.-33-99T>A		intron_variant
SRP54	XM_011537106.1	c.-33-99T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRP54	ENST00000216774.11	c.-33-99T>A		intron_variant		1	NM_003136.4	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26298 AN: 152026 Hom.: 2755 Cov.: 32

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

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.: 32 AF XY: 0.178 AC XY: 13274 AN XY: 74374

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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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

Other links and lift over

dbSNP: rs2273158; hg19: chr14-35465784; COSMIC: COSV53741668; COSMIC: COSV53741668;