NM_003134.6:c.54G>C

Variant summary

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

The NM_003134.6(SRP14):​c.54G>C​(p.Gln18His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,613,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

SRP14
NM_003134.6 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89
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=0.08198136).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRP14NM_003134.6 linkc.54G>C p.Gln18His missense_variant Exon 2 of 5 ENST00000267884.11 NP_003125.3 P37108
SRP14NM_001309434.1 linkc.-131G>C 5_prime_UTR_variant Exon 2 of 6 NP_001296363.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRP14ENST00000267884.11 linkc.54G>C p.Gln18His missense_variant Exon 2 of 5 1 NM_003134.6 ENSP00000267884.6 P37108

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152136
Hom.:
0
Cov.:
32
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:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000142
AC:
35
AN:
247210
Hom.:
0
AF XY:
0.000171
AC XY:
23
AN XY:
134550
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:
0.00112
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000167
GnomAD4 exome
AF:
0.0000630
AC:
92
AN:
1460974
Hom.:
0
Cov.:
32
AF XY:
0.0000894
AC XY:
65
AN XY:
726796
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:
0.00101
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000829
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152254
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74440
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:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.000149
AC:
18

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.54G>C (p.Q18H) alteration is located in exon 2 (coding exon 2) of the SRP14 gene. This alteration results from a G to C substitution at nucleotide position 54, causing the glutamine (Q) at amino acid position 18 to be replaced by a histidine (H). 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
Pathogenic
0.95
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;T
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.058
D
MetaRNN
Benign
0.082
T;T
MetaSVM
Benign
-0.38
T
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-3.3
D;D
REVEL
Benign
0.27
Sift
Uncertain
0.025
D;D
Sift4G
Uncertain
0.010
D;D
Polyphen
1.0
D;.
Vest4
0.47
MutPred
0.49
Loss of MoRF binding (P = 0.0924);Loss of MoRF binding (P = 0.0924);
MVP
0.50
MPC
1.4
ClinPred
0.90
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.82
gMVP
0.69

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: rs577332619; hg19: chr15-40331120; API