NM_018228.3:c.853C>T

Variant summary

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

The NM_018228.3(VRTN):​c.853C>T​(p.Leu285Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,880 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

VRTN
NM_018228.3 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33
Variant links:
Genes affected
VRTN (HGNC:20223): (vertebrae development associated) Predicted to enable sequence-specific DNA binding activity and transposase activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in chromatin. [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=0.25838986).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VRTNNM_018228.3 linkc.853C>T p.Leu285Phe missense_variant Exon 2 of 2 ENST00000256362.5 NP_060698.2 Q9H8Y1
VRTNXM_011536911.3 linkc.853C>T p.Leu285Phe missense_variant Exon 3 of 3 XP_011535213.1 Q9H8Y1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VRTNENST00000256362.5 linkc.853C>T p.Leu285Phe missense_variant Exon 2 of 2 1 NM_018228.3 ENSP00000256362.4 Q9H8Y1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152246
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
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:
6.84e-7
AC:
1
AN:
1461634
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727132
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152246
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.0000482
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
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.853C>T (p.L285F) alteration is located in exon 2 (coding exon 1) of the VRTN gene. This alteration results from a C to T substitution at nucleotide position 853, causing the leucine (L) at amino acid position 285 to be replaced by a phenylalanine (F). 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
0.19
BayesDel_addAF
Benign
-0.012
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.29
T
Eigen
Benign
0.032
Eigen_PC
Benign
0.010
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.069
D
MetaRNN
Benign
0.26
T
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-2.9
D
REVEL
Benign
0.25
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.41
B
Vest4
0.18
MutPred
0.64
Loss of disorder (P = 0.1194);
MVP
0.17
MPC
1.1
ClinPred
0.99
D
GERP RS
3.4
Varity_R
0.70
gMVP
0.42

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: rs1331864315; hg19: chr14-74824339; API