Variant 17-75136245-C-A details in Genebe, Genetics Data Aggregator

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

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]

JPT1 links:

LOC107985034 (HGNC:):

LOC107985034 links:

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
JPT1	NM_016185.4 linkuse as main transcript	c.322G>T	p.Val108Leu	missense_variant	5/5	ENST00000409753.8
LOC107985034	XR_007065907.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPT1	ENST00000409753.8 linkuse as main transcript	c.322G>T	p.Val108Leu	missense_variant	5/5	1	NM_016185.4	P1	Q9UK76-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152102

Hom.:

Cov.:

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:

AN:

228548

Hom.:

AF XY:

0.0000160

AC XY:

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:

AN:

1424598

Hom.:

Cov.:

AF XY:

0.00000567

AC XY:

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:

AN:

152102

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

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:

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 submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The 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

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

LIST_S2

Benign

0.49

M_CAP

Benign

0.017

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.10

REVEL

Benign

0.050

Sift

Benign

0.14

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.15

MutPred

0.25

Gain of methylation at K100 (P = 0.0251);

MVP

0.22

MPC

0.26

ClinPred

0.33

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over