rs1904294

chr10-63207685-A-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_032776.3(JMJD1C):c.3984T>A(p.Arg1328=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,614,178 control chromosomes in the GnomAD database, including 802,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.99 (73951 hom., cov: 32)
  • Exomes 𝑓: 1.0 (728822 hom.)
• Consequence: JMJD1C NM_032776.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.300

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-63207685-A-T is Benign according to our data. Variant chr10-63207685-A-T is described in ClinVar as [Benign]. Clinvar id is 1169949.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD1C	NM_032776.3	c.3984T>A	p.Arg1328=	synonymous_variant	10/26	ENST00000399262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000399262.7	c.3984T>A	p.Arg1328=	synonymous_variant	10/26	5	NM_032776.3
JMJD1C	ENST00000542921.5	c.3438T>A	p.Arg1146=	synonymous_variant	9/25	1		P1
JMJD1C	ENST00000402544.5	n.3956T>A		non_coding_transcript_exon_variant	7/22	1
JMJD1C	ENST00000327520.7	c.42T>A	p.Arg14=	synonymous_variant	1/12	2

Frequencies

GnomAD3 genomes AF: 0.985 AC: 149953 AN: 152208 Hom.: 73899 Cov.: 32

Gnomad AFR AF: 0.948

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.995

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.987

GnomAD3 exomes AF: 0.996 AC: 248158 AN: 249152 Hom.: 123603 AF XY: 0.997 AC XY: 134744 AN XY: 135160

Gnomad AFR exome AF: 0.944

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.999

GnomAD4 exome AF: 0.999 AC: 1459678 AN: 1461852 Hom.: 728822 Cov.: 65 AF XY: 0.999 AC XY: 726254 AN XY: 727228

Gnomad4 AFR exome AF: 0.946

Gnomad4 AMR exome AF: 0.997

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.997

GnomAD4 genome AF: 0.985 AC: 150064 AN: 152326 Hom.: 73951 Cov.: 32 AF XY: 0.986 AC XY: 73415 AN XY: 74476

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.995

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.987

Alfa AF: 0.941 Hom.: 21657

Bravo AF: 0.983

Asia WGS AF: 0.997 AC: 3467 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early myoclonic encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	7.3
Dann	Benign	0.84

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: rs1904294; hg19: chr10-64967445;