rs112116567

Positions:

• chr10-63214130-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_032776.3(JMJD1C):​c.2037T>C​(p.His679=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000933 in 1,614,186 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (9 hom.)
• Consequence: JMJD1C NM_032776.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.26

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 10-63214130-A-G is Benign according to our data. Variant chr10-63214130-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 529722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.26 with no splicing effect.
• BS2: High AC in GnomAd4 at 110 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD1C	NM_032776.3	c.2037T>C	p.His679=	synonymous_variant	8/26	ENST00000399262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000399262.7	c.2037T>C	p.His679=	synonymous_variant	8/26	5	NM_032776.3
JMJD1C	ENST00000542921.5	c.1491T>C	p.His497=	synonymous_variant	7/25	1		P1
JMJD1C	ENST00000402544.5	n.2009T>C		non_coding_transcript_exon_variant	5/22	1

Frequencies

GnomAD3 genomes AF: 0.000710 AC: 108 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000956 AC: 238 AN: 249062 Hom.: 3 AF XY: 0.00104 AC XY: 141 AN XY: 135094

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.000608

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00232

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.000931

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.000955 AC: 1396 AN: 1461870 Hom.: 9 Cov.: 33 AF XY: 0.00103 AC XY: 746 AN XY: 727230

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000604

Gnomad4 ASJ exome AF: 0.00214

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00224

Gnomad4 FIN exome AF: 0.000243

Gnomad4 NFE exome AF: 0.000869

Gnomad4 OTH exome AF: 0.00139

GnomAD4 genome AF: 0.000722 AC: 110 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000698 AC XY: 52 AN XY: 74478

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000926

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00116 Hom.: 1

Bravo AF: 0.000740

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00153

EpiControl AF: 0.00136

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

JMJD1C: BS1, BS2 -

Early myoclonic encephalopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 10, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.3
DANN	Benign	0.61

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: rs112116567; hg19: chr10-64973890; COSMIC: COSV67868400; COSMIC: COSV67868400;