chr14-34999426-C-T

Position:

• chr14-34999426-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.79-132C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 588,948 control chromosomes in the GnomAD database, including 49,588 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (10918 hom., cov: 31)
  • Exomes 𝑓: 0.41 (38670 hom.)
• Consequence: SRP54 NM_003136.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.117

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 14-34999426-C-T is Benign according to our data. Variant chr14-34999426-C-T is described in ClinVar as [Benign]. Clinvar id is 1294954.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRP54	NM_003136.4	c.79-132C>T		intron_variant		ENST00000216774.11	NP_003127.1
SRP54	NM_001146282.2	c.24-1510C>T		intron_variant			NP_001139754.1
SRP54	NM_001411017.1	c.79-132C>T		intron_variant			NP_001397946.1
SRP54	XM_011537106.1	c.79-132C>T		intron_variant			XP_011535408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRP54	ENST00000216774.11	c.79-132C>T		intron_variant		1	NM_003136.4	ENSP00000216774.6

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55921 AN: 151792 Hom.: 10909 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.364

GnomAD4 exome AF: 0.406 AC: 177286 AN: 437038 Hom.: 38670 AF XY: 0.406 AC XY: 93843 AN XY: 230864

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.330

Gnomad4 ASJ exome AF: 0.383

Gnomad4 EAS exome AF: 0.737

Gnomad4 SAS exome AF: 0.430

Gnomad4 FIN exome AF: 0.477

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.368 AC: 55967 AN: 151910 Hom.: 10918 Cov.: 31 AF XY: 0.378 AC XY: 28046 AN XY: 74240

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.368

Alfa AF: 0.367 Hom.: 1297

Bravo AF: 0.353

Asia WGS AF: 0.556 AC: 1931 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 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs28627922; hg19: chr14-35468632;