11-122946550-T-C

Position:

chr11-122946550-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024806.4(JHY):c.1687T>C(p.Trp563Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

JHY
NM_024806.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.211

Variant links:

Genes affected

JHY (HGNC:26288): (junctional cadherin complex regulator) Predicted to be involved in axoneme assembly and brain development. Predicted to act upstream of or within several processes, including cerebrospinal fluid circulation; motile cilium assembly; and regulation of establishment of planar polarity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

JHY links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02208817).

BP6

Variant 11-122946550-T-C is Benign according to our data. Variant chr11-122946550-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3112312.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
JHY	NM_024806.4 linkuse as main transcript	c.1687T>C	p.Trp563Arg	missense_variant	6/9	ENST00000227349.7	NP_079082.2
JHY	NM_001363089.2 linkuse as main transcript	c.1687T>C	p.Trp563Arg	missense_variant	6/9		NP_001350018.1
JHY	NM_001363087.2 linkuse as main transcript	c.1687T>C	p.Trp563Arg	missense_variant	6/8		NP_001350016.1
JHY	NM_001363088.2 linkuse as main transcript	c.1573T>C	p.Trp525Arg	missense_variant	5/8		NP_001350017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JHY	ENST00000227349.7 linkuse as main transcript	c.1687T>C	p.Trp563Arg	missense_variant	6/9	1	NM_024806.4	ENSP00000227349	P1	Q6NUN7-1
JHY	ENST00000531316.1 linkuse as main transcript	c.1687T>C	p.Trp563Arg	missense_variant	5/8	2		ENSP00000431669	P1	Q6NUN7-1
JHY	ENST00000534362.1 linkuse as main transcript	n.89T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152098

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

250122

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135092

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461198

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726808

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:

0.00000989

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000936

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.59

DANN

Benign

0.23

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.36

T;.

M_CAP

Benign

0.0037

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

1.5

N;N

REVEL

Benign

0.026

Sift

Benign

0.95

T;T

Sift4G

Benign

0.75

T;T

Polyphen

0.0

B;B

Vest4

0.029

MutPred

0.39

Gain of disorder (P = 0.0013);Gain of disorder (P = 0.0013);

MVP

0.12

MPC

0.19

ClinPred

0.043

GERP RS

2.8

Varity_R

0.036

gMVP

0.072

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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