dbSNP rs749130159: SRP14:p.Pro124_Ala127del (chr15-40036362-CTGCTGTTGTTGG-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_003134.6(SRP14):c.370_381delCCAACAACAGCA(p.Pro124_Ala127del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,613,534 control chromosomes in the GnomAD database, including 27 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 25 hom. )

Consequence

SRP14
NM_003134.6 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.33

Variant links:

Genes affected

SRP14 (HGNC:11299): (signal recognition particle 14) Enables RNA binding activity. Involved in protein targeting to ER. Located in nucleus. Part of signal recognition particle, endoplasmic reticulum targeting. [provided by Alliance of Genome Resources, Apr 2022]

SRP14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 15-40036362-CTGCTGTTGTTGG-C is Benign according to our data. Variant chr15-40036362-CTGCTGTTGTTGG-C is described in ClinVar as [Likely_benign]. Clinvar id is 2645164.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00338 (4941/1461342) while in subpopulation MID AF= 0.0342 (197/5766). AF 95% confidence interval is 0.0303. There are 25 homozygotes in gnomad4_exome. There are 2551 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd4 at 503 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRP14	NM_003134.6 link	c.370_381delCCAACAACAGCA	p.Pro124_Ala127del	conservative_inframe_deletion	Exon 5 of 5	ENST00000267884.11	NP_003125.3	P37108
SRP14	NM_001309434.1 link	c.226_237delCCAACAACAGCA	p.Pro76_Ala79del	conservative_inframe_deletion	Exon 6 of 6		NP_001296363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRP14	ENST00000267884.11 link	c.370_381delCCAACAACAGCA	p.Pro124_Ala127del	conservative_inframe_deletion	Exon 5 of 5	1	NM_003134.6	ENSP00000267884.6		P37108

Frequencies

GnomAD3 genomes

AF:

0.00331

AC:

504

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.000970

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00303

Gnomad OTH

AF:

0.00672

GnomAD3 exomes

AF:

0.00368

AC:

925

AN:

251264

Hom.:

AF XY:

0.00386

AC XY:

524

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00303

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.0174

Gnomad EAS exome

AF:

0.000762

Gnomad SAS exome

AF:

0.00350

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00362

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00338

AC:

4941

AN:

1461342

Hom.:

AF XY:

0.00351

AC XY:

2551

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.00323

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.0171

Gnomad4 EAS exome

AF:

0.000630

Gnomad4 SAS exome

AF:

0.00382

Gnomad4 FIN exome

AF:

0.00157

Gnomad4 NFE exome

AF:

0.00302

Gnomad4 OTH exome

AF:

0.00427

GnomAD4 genome

AF:

0.00331

AC:

503

AN:

152192

Hom.:

Cov.:

AF XY:

0.00351

AC XY:

261

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00294

Gnomad4 AMR

AF:

0.00517

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.000972

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.00303

Gnomad4 OTH

AF:

0.00665

Alfa

AF:

0.00373

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SRP14: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over