rs17510813

Variant names:

• chr14-35028060-C-T
• rs17510813
• NM_003136.4:c.1328-28C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-35028060-C-T
• chr14-35028060-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.477
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• neutropenia, severe congenital, 8, autosomal dominant

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• autosomal dominant severe congenital neutropenia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Shwachman-Diamond syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003136.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP54	NM_003136.4	MANE Select	c.1328-28C>T		intron	N/A	NP_003127.1	P61011-1
	SRP54	NM_001440813.1		c.1328-28C>T		intron	N/A	NP_001427742.1
	SRP54	NM_001146282.2		c.1181-28C>T		intron	N/A	NP_001139754.1	P61011-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP54	ENST00000216774.11	TSL:1 MANE Select	c.1328-28C>T		intron	N/A	ENSP00000216774.6	P61011-1
	SRP54	ENST00000859405.1		c.1379-28C>T		intron	N/A	ENSP00000529464.1
	SRP54	ENST00000556994.5	TSL:5	c.1328-28C>T		intron	N/A	ENSP00000451818.1	P61011-1

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

GnomAD2 exomes AF: 0.0853 AC: 20498 AN: 240276 AF XY: 0.0903

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 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

African (AFR) AF: 0.0176 AC: 549 AN: 31234

American (AMR) AF: 0.0538 AC: 2234 AN: 41544

Ashkenazi Jewish (ASJ) AF: 0.0676 AC: 1704 AN: 25190

East Asian (EAS) AF: 0.000331 AC: 13 AN: 39266

South Asian (SAS) AF: 0.102 AC: 8383 AN: 82114

European-Finnish (FIN) AF: 0.0638 AC: 3379 AN: 52926

Middle Eastern (MID) AF: 0.114 AC: 629 AN: 5526

European-Non Finnish (NFE) AF: 0.122 AC: 126225 AN: 1034788

Other (OTH) AF: 0.0974 AC: 5554 AN: 57030

GnomAD4 genome AF: 0.0772 AC: 11727 AN: 151958 Hom.: 601 Cov.: 31 AF XY: 0.0742 AC XY: 5506 AN XY: 74246

African (AFR) AF: 0.0194 AC: 805 AN: 41484

American (AMR) AF: 0.0677 AC: 1032 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.0692 AC: 240 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5180

South Asian (SAS) AF: 0.0969 AC: 467 AN: 4818

European-Finnish (FIN) AF: 0.0551 AC: 578 AN: 10488

Middle Eastern (MID) AF: 0.100 AC: 29 AN: 290

European-Non Finnish (NFE) AF: 0.122 AC: 8314 AN: 67978

Other (OTH) AF: 0.0731 AC: 154 AN: 2106

Alfa AF: 0.111 Hom.: 1748

Bravo AF: 0.0746

Asia WGS AF: 0.0380 AC: 135 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.23
DANN	Benign	0.55
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17510813; hg19: chr14-35497266;