Variant 11-122959365-T-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 ENST00000227349.7(JHY):c.2257T>A(p.Ser753Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

JHY
ENST00000227349.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.778

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=0.06927171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JHY	NM_024806.4 linkuse as main transcript	c.2257T>A	p.Ser753Thr	missense_variant	9/9	ENST00000227349.7	NP_079082.2	Q6NUN7-1
JHY	NM_001363089.2 linkuse as main transcript	c.2257T>A	p.Ser753Thr	missense_variant	9/9		NP_001350018.1
JHY	NM_001363087.2 linkuse as main transcript	c.2176T>A	p.Ser726Thr	missense_variant	8/8		NP_001350016.1
JHY	NM_001363088.2 linkuse as main transcript	c.2143T>A	p.Ser715Thr	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.2257T>A	p.Ser753Thr	missense_variant	9/9	1	NM_024806.4	ENSP00000227349.2		Q6NUN7-1
JHY	ENST00000531316.1 linkuse as main transcript	c.2257T>A	p.Ser753Thr	missense_variant	8/8	2		ENSP00000431669.1		Q6NUN7-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251282

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.000185

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

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

Oct 12, 2021

The c.2257T>A (p.S753T) alteration is located in exon 9 (coding exon 8) of the C11orf63 gene. This alteration results from a T to A substitution at nucleotide position 2257, causing the serine (S) at amino acid position 753 to be replaced by a threonine (T). 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

0.096

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.044

T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.046

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.60

T;.

M_CAP

Benign

0.0051

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

N;N

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.067

Sift

Uncertain

0.018

D;D

Sift4G

Benign

0.52

T;T

Polyphen

0.21

B;B

Vest4

0.044

MVP

0.50

MPC

0.43

ClinPred

0.35

GERP RS

3.0

Varity_R

0.078

gMVP

0.34

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