Variant 15-40036374-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003134.6(SRP14):c.370C>G(p.Pro124Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,612,888 control chromosomes in the GnomAD database, including 669,823 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.90 ( 61516 hom., cov: 35)

Exomes 𝑓: 0.91 ( 608307 hom. )

Consequence

SRP14
NM_003134.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.715

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:

SRP14 (HGNC:):

SRP14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.785058E-7).

BP6

Variant 15-40036374-G-C is Benign according to our data. Variant chr15-40036374-G-C is described in ClinVar as [Benign]. Clinvar id is 402822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRP14	NM_003134.6 linkuse as main transcript	c.370C>G	p.Pro124Ala	missense_variant	5/5	ENST00000267884.11	NP_003125.3	P37108
SRP14	NM_001309434.1 linkuse as main transcript	c.226C>G	p.Pro76Ala	missense_variant	6/6		NP_001296363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRP14	ENST00000267884.11 linkuse as main transcript	c.370C>G	p.Pro124Ala	missense_variant	5/5	1	NM_003134.6	ENSP00000267884.6		P37108

Frequencies

GnomAD3 genomes

AF:

0.899

AC:

136680

AN:

151990

Hom.:

61479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.861

Gnomad AMI

AF:

0.950

Gnomad AMR

AF:

0.935

Gnomad ASJ

AF:

0.886

Gnomad EAS

AF:

0.769

Gnomad SAS

AF:

0.901

Gnomad FIN

AF:

0.904

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.923

Gnomad OTH

AF:

0.905

GnomAD3 exomes

AF:

0.904

AC:

227301

AN:

251320

Hom.:

103114

AF XY:

0.904

AC XY:

122852

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.861

Gnomad AMR exome

AF:

0.960

Gnomad ASJ exome

AF:

0.869

Gnomad EAS exome

AF:

0.759

Gnomad SAS exome

AF:

0.896

Gnomad FIN exome

AF:

0.908

Gnomad NFE exome

AF:

0.921

Gnomad OTH exome

AF:

0.912

GnomAD4 exome

AF:

0.912

AC:

1332618

AN:

1460782

Hom.:

608307

Cov.:

AF XY:

0.912

AC XY:

662410

AN XY:

726690

show subpopulations

Gnomad4 AFR exome

AF:

0.861

Gnomad4 AMR exome

AF:

0.958

Gnomad4 ASJ exome

AF:

0.874

Gnomad4 EAS exome

AF:

0.753

Gnomad4 SAS exome

AF:

0.895

Gnomad4 FIN exome

AF:

0.908

Gnomad4 NFE exome

AF:

0.921

Gnomad4 OTH exome

AF:

0.895

GnomAD4 genome

AF:

0.899

AC:

136772

AN:

152106

Hom.:

61516

Cov.:

AF XY:

0.897

AC XY:

66712

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.861

Gnomad4 AMR

AF:

0.936

Gnomad4 ASJ

AF:

0.886

Gnomad4 EAS

AF:

0.768

Gnomad4 SAS

AF:

0.902

Gnomad4 FIN

AF:

0.904

Gnomad4 NFE

AF:

0.923

Gnomad4 OTH

AF:

0.905

Alfa

AF:

0.916

Hom.:

10170

Bravo

AF:

0.899

TwinsUK

AF:

0.921

AC:

3414

ALSPAC

AF:

0.917

AC:

3533

ESP6500AA

AF:

0.873

AC:

3845

ESP6500EA

AF:

0.926

AC:

7966

ExAC

AF:

0.904

AC:

109692

Asia WGS

AF:

0.826

AC:

2874

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.0

DANN

Benign

0.34

DEOGEN2

Benign

0.038

T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.24

T;.;T

MetaRNN

Benign

7.8e-7

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.19

N;N;N

REVEL

Benign

0.042

Sift

Benign

1.0

T;.;.

Sift4G

Benign

0.92

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.060

MPC

0.49

ClinPred

0.00092

GERP RS

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.060

gMVP

0.084

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

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