10-63168092-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032776.3(JMJD1C):c.7576G>C(p.Ala2526Pro) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: JMJD1C NM_032776.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0430

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]

ACMG classification

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=0.17577341).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD1C	NM_032776.3	c.7576G>C	p.Ala2526Pro	missense_variant	26/26	ENST00000399262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000399262.7	c.7576G>C	p.Ala2526Pro	missense_variant	26/26	5	NM_032776.3
JMJD1C	ENST00000542921.5	c.7030G>C	p.Ala2344Pro	missense_variant	25/25	1		P1
JMJD1C	ENST00000402544.5	n.7267G>C		non_coding_transcript_exon_variant	22/22	1
JMJD1C	ENST00000467356.5	n.434G>C		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Apr 19, 2023

Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
Cadd	Benign	15
Dann	Uncertain	0.99
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.39	T
Polyphen		0.68	.;P;.
Vest4		0.57, 0.53
MutPred		0.29		.;Gain of methylation at K2521 (P = 0.0444);.;
MVP		0.84
MPC		1.6
ClinPred		0.81	D
GERP RS		-0.77
Varity_R		0.26
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-64927852;