rs9322942

chr14-35022137-T-Achr14-35022137-T-Cchr14-35022137-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003136.4(SRP54):c.1157-773T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,694 control chromosomes in the GnomAD database, including 9,629 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (9629 hom., cov: 31)
• Consequence: SRP54 NM_003136.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• 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	UniProt
SRP54	NM_003136.4	c.1157-773T>A		intron_variant		ENST00000216774.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRP54	ENST00000216774.11	c.1157-773T>A		intron_variant		1	NM_003136.4	P1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52324 AN: 151580 Hom.: 9622 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.339

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.345 AC: 52369 AN: 151694 Hom.: 9629 Cov.: 31 AF XY: 0.354 AC XY: 26242 AN XY: 74048

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.343

Alfa AF: 0.339 Hom.: 1093

Bravo AF: 0.331

Asia WGS AF: 0.544 AC: 1889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	8.2
Dann	Benign	0.68

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: rs9322942; hg19: chr14-35491343;