chr15-40036407-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003134.6(SRP14):​c.337G>A​(p.Ala113Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SRP14
NM_003134.6 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.833
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.077077836).
BS2
High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRP14NM_003134.6 linkc.337G>A p.Ala113Thr missense_variant Exon 5 of 5 ENST00000267884.11 NP_003125.3 P37108
SRP14NM_001309434.1 linkc.193G>A p.Ala65Thr missense_variant Exon 6 of 6 NP_001296363.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRP14ENST00000267884.11 linkc.337G>A p.Ala113Thr missense_variant Exon 5 of 5 1 NM_003134.6 ENSP00000267884.6 P37108

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
33
show subpopulations
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250866
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135804
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000151
AC:
22
AN:
1460996
Hom.:
0
Cov.:
76
AF XY:
0.0000151
AC XY:
11
AN XY:
726768
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000349
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000480
Hom.:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.337G>A (p.A113T) alteration is located in exon 5 (coding exon 5) of the SRP14 gene. This alteration results from a G to A substitution at nucleotide position 337, causing the alanine (A) at amino acid position 113 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
3.7
DANN
Benign
0.54
DEOGEN2
Benign
0.063
T;.;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.43
T;.;T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.077
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.0
N;.;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.16
N;N;N
REVEL
Benign
0.041
Sift
Uncertain
0.0080
D;.;.
Sift4G
Uncertain
0.042
D;D;D
Polyphen
0.0
B;.;.
Vest4
0.14
MutPred
0.31
Gain of glycosylation at A113 (P = 0.0017);.;.;
MVP
0.31
MPC
0.49
ClinPred
0.081
T
GERP RS
-0.47
Varity_R
0.072
gMVP
0.14

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.

Other links and lift over

dbSNP: rs754073133; hg19: chr15-40328608; API