Variant 16-1678334-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_144570.3(JPT2):c.22G>A(p.Glu8Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,235,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

JPT2
NM_144570.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

Variant links:

Genes affected

JPT2 (HGNC:14137): (Jupiter microtubule associated homolog 2) Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

JPT2 links:

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=0.11219779).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPT2	NM_144570.3 linkuse as main transcript	c.22G>A	p.Glu8Lys	missense_variant	1/5	ENST00000248098.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPT2	ENST00000248098.8 linkuse as main transcript	c.22G>A	p.Glu8Lys	missense_variant	1/5	1	NM_144570.3	P1	Q9H910-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000369

AC:

AN:

1083334

Hom.:

Cov.:

AF XY:

0.0000469

AC XY:

AN XY:

512036

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000232

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000509

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000348

Gnomad4 OTH exome

AF:

0.0000919

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151886

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

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

Feb 06, 2023

The c.22G>A (p.E8K) alteration is located in exon 1 (coding exon 1) of the HN1L gene. This alteration results from a G to A substitution at nucleotide position 22, causing the glutamic acid (E) at amino acid position 8 to be replaced by a lysine (K). 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

0.14

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;.;T;.;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.50

T;T;T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.11

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.0

N;N;N;N;N

REVEL

Benign

0.071

Sift

Uncertain

0.027

D;D;D;D;D

Sift4G

Benign

0.37

T;D;T;T;D

Polyphen

0.88

P;.;.;.;B

Vest4

0.15

MutPred

0.27

Gain of MoRF binding (P = 8e-04);Gain of MoRF binding (P = 8e-04);Gain of MoRF binding (P = 8e-04);Gain of MoRF binding (P = 8e-04);Gain of MoRF binding (P = 8e-04);

MVP

0.093

MPC

0.56

ClinPred

0.19

GERP RS

2.3

Varity_R

0.068

gMVP

0.40

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.

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