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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003134.6(SRP14):c.370C>A(p.Pro124Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P124A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 35)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SRP14
NM_003134.6 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06042111).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRP14	NM_003134.6 linkuse as main transcript	c.370C>A	p.Pro124Thr	missense_variant	5/5	ENST00000267884.11	NP_003125.3	P37108
SRP14	NM_001309434.1 linkuse as main transcript	c.226C>A	p.Pro76Thr	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>A	p.Pro124Thr	missense_variant	5/5	1	NM_003134.6	ENSP00000267884.6		P37108

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152000

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460774

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152000

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74242

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.5

DANN

Benign

0.19

DEOGEN2

Benign

0.038

T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.28

T;.;T

M_CAP

Benign

0.0010

MetaRNN

Benign

0.060

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.14

N;D;D

REVEL

Benign

0.036

Sift

Benign

0.050

D;.;.

Sift4G

Benign

0.34

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.068

MutPred

0.16

Loss of loop (P = 0.0075);.;.;

MVP

0.27

MPC

0.57

ClinPred

0.048

GERP RS

0.23

Varity_R

0.15

gMVP

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over