rs200242659

Positions:

• chr10-63206861-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_032776.3(JMJD1C):​c.4808T>C​(p.Ile1603Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000407 in 1,606,810 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (1 hom.)
• Consequence: JMJD1C NM_032776.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.03

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013678908).
• BP6: Variant 10-63206861-A-G is Benign according to our data. Variant chr10-63206861-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 580833.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.4808T>C	p.Ile1603Thr	missense_variant	10/26	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.4808T>C	p.Ile1603Thr	missense_variant	10/26	5	NM_032776.3	ENSP00000382204
JMJD1C	ENST00000542921.5	c.4262T>C	p.Ile1421Thr	missense_variant	9/25	1		ENSP00000444682	P1
JMJD1C	ENST00000402544.5	n.4780T>C		non_coding_transcript_exon_variant	7/22	1
JMJD1C	ENST00000327520.7	c.866T>C	p.Ile289Thr	missense_variant	1/12	2		ENSP00000335929

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000466 AC: 114 AN: 244530 Hom.: 1 AF XY: 0.000498 AC XY: 66 AN XY: 132628

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.0000893

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000844

Gnomad NFE exome AF: 0.000789

Gnomad OTH exome AF: 0.000509

GnomAD4 exome AF: 0.000421 AC: 613 AN: 1454532 Hom.: 1 Cov.: 31 AF XY: 0.000388 AC XY: 281 AN XY: 723394

Gnomad4 AFR exome AF: 0.000151

Gnomad4 AMR exome AF: 0.000160

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000717

Gnomad4 NFE exome AF: 0.000485

Gnomad4 OTH exome AF: 0.000416

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74466

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000530 Hom.: 0

Bravo AF: 0.000298

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000244 AC: 2

ExAC AF: 0.000637 AC: 77

EpiCase AF: 0.000273

EpiControl AF: 0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early myoclonic encephalopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.85
DEOGEN2	Benign	0.014	.;T;.
Eigen	Benign	0.0060
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.014	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	.;N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.64	.;N;N
REVEL	Benign	0.046
Sift	Benign	0.40	.;T;T
Sift4G	Benign	0.57	.;T;T
Polyphen		0.0010	.;B;.
Vest4		0.046, 0.075
MVP		0.11
MPC		0.082
ClinPred		0.0047	T
GERP RS		4.1
Varity_R		0.023
gMVP		0.036

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

Other links and lift over

dbSNP: rs200242659; hg19: chr10-64966621; COSMIC: COSV59515119;