rs1904294

Variant names:

• chr10-63207685-A-T
• rs1904294
• NM_032776.3:c.3984T>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_032776.3(JMJD1C):​c.3984T>A​(p.Arg1328Arg) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.300
• Publications: 19 publications found

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

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.077).
• BP6: Variant 10-63207685-A-T is Benign according to our data. Variant chr10-63207685-A-T is described in ClinVar as Benign. ClinVar VariationId is 1169949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	NM_032776.3	MANE Select	c.3984T>A	p.Arg1328Arg	synonymous	Exon 10 of 26	NP_116165.1
	JMJD1C	NM_001322252.2		c.3870T>A	p.Arg1290Arg	synonymous	Exon 9 of 25	NP_001309181.1
	JMJD1C	NM_001282948.2		c.3438T>A	p.Arg1146Arg	synonymous	Exon 9 of 25	NP_001269877.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.3984T>A	p.Arg1328Arg	synonymous	Exon 10 of 26	ENSP00000382204.2
	JMJD1C	ENST00000542921.5	TSL:1	c.3438T>A	p.Arg1146Arg	synonymous	Exon 9 of 25	ENSP00000444682.1
	JMJD1C	ENST00000402544.5	TSL:1	n.3956T>A		non_coding_transcript_exon	Exon 7 of 22

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

GnomAD2 exomes AF: 0.996 AC: 248158 AN: 249152 AF XY: 0.997

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 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

African (AFR) AF: 0.946 AC: 31683 AN: 33480

American (AMR) AF: 0.997 AC: 44593 AN: 44722

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26134 AN: 26134

East Asian (EAS) AF: 1.00 AC: 39698 AN: 39698

South Asian (SAS) AF: 1.00 AC: 86242 AN: 86256

European-Finnish (FIN) AF: 1.00 AC: 53408 AN: 53408

Middle Eastern (MID) AF: 0.999 AC: 5760 AN: 5768

European-Non Finnish (NFE) AF: 1.00 AC: 1111962 AN: 1111990

Other (OTH) AF: 0.997 AC: 60198 AN: 60396

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

African (AFR) AF: 0.948 AC: 39413 AN: 41566

American (AMR) AF: 0.995 AC: 15229 AN: 15300

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 1.00 AC: 4819 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68028 AN: 68038

Other (OTH) AF: 0.987 AC: 2089 AN: 2116

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Early myoclonic encephalopathy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.3
DANN	Benign	0.84
PhyloP100		0.30
PromoterAI		-0.034	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1904294; hg19: chr10-64967445; COSMIC: COSV108170046;