Genetic Variant JMJD1C:p.Thr1390Lys (chr10-63207500-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032776.3(JMJD1C):c.4169C>A(p.Thr1390Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1390M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

JMJD1C
NM_032776.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.997

Publications

1 publications found

Variant links:

Genes affected

JMJD1C (HGNC:12313): (jumonji domain containing 1C) The protein encoded by this gene interacts with thyroid hormone receptors and contains a jumonji domain. It is a candidate histone demethylase and is thought to be a coactivator for key transcription factors. It plays a role in the DNA-damage response pathway by demethylating the mediator of DNA damage checkpoint 1 (MDC1) protein, and is required for the survival of acute myeloid leukemia. Mutations in this gene are associated with Rett syndrome and intellectual disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

JMJD1C Gene-Disease associations (from GenCC):

22q11.2 deletion syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Illumina
neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: G2P

JMJD1C links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04625258).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032776.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
JMJD1C	NM_032776.3	MANE Select	c.4169C>A	p.Thr1390Lys	missense	Exon 10 of 26	NP_116165.1
JMJD1C	NM_001322252.2		c.4055C>A	p.Thr1352Lys	missense	Exon 9 of 25	NP_001309181.1
JMJD1C	NM_001282948.2		c.3623C>A	p.Thr1208Lys	missense	Exon 9 of 25	NP_001269877.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.4169C>A	p.Thr1390Lys	missense	Exon 10 of 26	ENSP00000382204.2
JMJD1C	ENST00000542921.5	TSL:1	c.3623C>A	p.Thr1208Lys	missense	Exon 9 of 25	ENSP00000444682.1
JMJD1C	ENST00000402544.5	TSL:1	n.4141C>A		non_coding_transcript_exon	Exon 7 of 22

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.015

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.75

M_CAP

Benign

0.0079

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.5

REVEL

Benign

0.082

Sift

Benign

0.088

Sift4G

Benign

0.92

Polyphen

0.0010

Vest4

0.083

MutPred

0.20

Gain of ubiquitination at T1390 (P = 0.0185)

MVP

0.25

MPC

0.079

ClinPred

0.021

GERP RS

1.2

PromoterAI

-0.085

Neutral

(source)

Varity_R

0.032

gMVP

0.28

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over