Variant 11-122959256-A-T 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_024806.4(JHY):c.2148A>T(p.Glu716Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,613,408 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

JHY
NM_024806.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

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 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=0.15165707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JHY	NM_024806.4 linkuse as main transcript	c.2148A>T	p.Glu716Asp	missense_variant	9/9	ENST00000227349.7	NP_079082.2	Q6NUN7-1
JHY	NM_001363089.2 linkuse as main transcript	c.2148A>T	p.Glu716Asp	missense_variant	9/9		NP_001350018.1
JHY	NM_001363087.2 linkuse as main transcript	c.2067A>T	p.Glu689Asp	missense_variant	8/8		NP_001350016.1
JHY	NM_001363088.2 linkuse as main transcript	c.2034A>T	p.Glu678Asp	missense_variant	8/8		NP_001350017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JHY	ENST00000227349.7 linkuse as main transcript	c.2148A>T	p.Glu716Asp	missense_variant	9/9	1	NM_024806.4	ENSP00000227349.2		Q6NUN7-1
JHY	ENST00000531316.1 linkuse as main transcript	c.2148A>T	p.Glu716Asp	missense_variant	8/8	2		ENSP00000431669.1		Q6NUN7-1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152196

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:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000120

AC:

AN:

250828

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135552

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000290

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:

0.000238

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000228

AC:

333

AN:

1461212

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

172

AN XY:

726892

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000286

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000171

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74358

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:

0.000382

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000297

Hom.:

Bravo

AF:

0.000147

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000437

EpiControl

AF:

0.000474

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 18, 2021

The c.2148A>T (p.E716D) alteration is located in exon 9 (coding exon 8) of the C11orf63 gene. This alteration results from a A to T substitution at nucleotide position 2148, causing the glutamic acid (E) at amino acid position 716 to be replaced by an aspartic acid (D). 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

0.25

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.084

T;T

Eigen

Benign

-0.017

Eigen_PC

Benign

0.062

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.65

T;.

M_CAP

Benign

0.018

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

0.65

D;D

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.077

Sift

Benign

0.21

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.74

P;P

Vest4

0.26

MutPred

0.11

Gain of MoRF binding (P = 0.126);Gain of MoRF binding (P = 0.126);

MVP

0.66

MPC

0.22

ClinPred

0.087

GERP RS

3.5

Varity_R

0.093

gMVP

0.26

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