chr15-75207166-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015492.5(C15orf39):​c.1118C>T​(p.Pro373Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,936 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

C15orf39
NM_015492.5 missense

Scores

1
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27
Variant links:
Genes affected
C15orf39 (HGNC:24497): (chromosome 15 open reading frame 39) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.099006295).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C15orf39NM_015492.5 linkc.1118C>T p.Pro373Leu missense_variant Exon 2 of 3 ENST00000394987.5 NP_056307.3 Q6ZRI6-1
C15orf39XM_047432864.1 linkc.1118C>T p.Pro373Leu missense_variant Exon 3 of 4 XP_047288820.1
C15orf39XM_047432865.1 linkc.284C>T p.Pro95Leu missense_variant Exon 4 of 5 XP_047288821.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C15orf39ENST00000394987.5 linkc.1118C>T p.Pro373Leu missense_variant Exon 2 of 3 1 NM_015492.5 ENSP00000378438.4 Q6ZRI6-1
C15orf39ENST00000567617.1 linkc.1118C>T p.Pro373Leu missense_variant Exon 1 of 2 1 ENSP00000458025.1 Q6ZRI6-2
C15orf39ENST00000360639.6 linkc.1118C>T p.Pro373Leu missense_variant Exon 2 of 3 2 ENSP00000353854.2 Q6ZRI6-1
C15orf39ENST00000565074.1 linkc.722C>T p.Pro241Leu missense_variant Exon 1 of 1 6 ENSP00000454405.1 H3BMJ2

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
152114
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.000628
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
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251360
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135866
show subpopulations
Gnomad AFR exome
AF:
0.000369
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461704
Hom.:
1
Cov.:
70
AF XY:
0.00000963
AC XY:
7
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.0000224
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.000177
AC:
27
AN:
152232
Hom.:
0
Cov.:
29
AF XY:
0.000202
AC XY:
15
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.000650
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
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.000144
ESP6500AA
AF:
0.000228
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 09, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1118C>T (p.P373L) alteration is located in exon 2 (coding exon 1) of the C15orf39 gene. This alteration results from a C to T substitution at nucleotide position 1118, causing the proline (P) at amino acid position 373 to be replaced by a leucine (L). 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
0.15
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.057
T;T;.
Eigen
Benign
0.0053
Eigen_PC
Benign
-0.084
FATHMM_MKL
Benign
0.40
N
LIST_S2
Benign
0.82
.;T;T
M_CAP
Benign
0.072
D
MetaRNN
Benign
0.099
T;T;T
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
1.9
L;L;L
PROVEAN
Pathogenic
-5.7
D;D;D
REVEL
Benign
0.20
Sift
Uncertain
0.0040
D;D;D
Sift4G
Uncertain
0.0040
D;D;D
Polyphen
0.90
P;P;.
Vest4
0.36
MVP
0.13
MPC
0.71
ClinPred
0.63
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.37

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: rs182425183; hg19: chr15-75499507; API