chr17-75136245-C-A

Variant summary

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

The NM_016185.4(JPT1):​c.322G>T​(p.Val108Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 1,576,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict 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: 0.0000063 ( 0 hom. )

Consequence

JPT1
NM_016185.4 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.996
Variant links:
Genes affected
JPT1 (HGNC:14569): (Jupiter microtubule associated homolog 1) Located in nuclear membrane; nucleolus; and nucleoplasm. [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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.02354902).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
JPT1NM_016185.4 linkuse as main transcriptc.322G>T p.Val108Leu missense_variant 5/5 ENST00000409753.8
LOC107985034XR_007065907.1 linkuse as main transcript upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
JPT1ENST00000409753.8 linkuse as main transcriptc.322G>T p.Val108Leu missense_variant 5/51 NM_016185.4 P1Q9UK76-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152102
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:
0.000385
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:
0.0000219
AC:
5
AN:
228548
Hom.:
0
AF XY:
0.0000160
AC XY:
2
AN XY:
125384
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000286
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:
0.00000632
AC:
9
AN:
1424598
Hom.:
0
Cov.:
33
AF XY:
0.00000567
AC XY:
4
AN XY:
705268
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000230
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152102
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 07, 2023The c.303G>T (p.M101I) alteration is located in exon 4 (coding exon 4) of the HN1 gene. This alteration results from a G to T substitution at nucleotide position 303, causing the methionine (M) at amino acid position 101 to be replaced by an isoleucine (I). 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
0.11
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
7.4
DANN
Uncertain
0.99
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.49
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.024
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;D;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.10
N
REVEL
Benign
0.050
Sift
Benign
0.14
T
Sift4G
Benign
0.17
T
Polyphen
0.0
B
Vest4
0.15
MutPred
0.25
Gain of methylation at K100 (P = 0.0251);
MVP
0.22
MPC
0.26
ClinPred
0.33
T
GERP RS
1.1
gMVP
0.040

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs747161676; hg19: chr17-73132340; API