rs141981100

Variant names:

• chr10-63214835-TTCA-T
• rs141981100
• NM_032776.3:c.1329_1331delTGA

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BS1 BS2

The NM_032776.3(JMJD1C):​c.1329_1331delTGA​(p.His443_Glu444delinsGln) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00593 in 1,614,008 control chromosomes in the GnomAD database, including 84 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (57 hom.)
• Consequence: JMJD1C NM_032776.3 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.09
• Publications: 1 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 -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_032776.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 10-63214835-TTCA-T is Benign according to our data. Variant chr10-63214835-TTCA-T is described in ClinVar as Benign. ClinVar VariationId is 460213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0131 (1991/152266) while in subpopulation AFR AF = 0.0337 (1398/41528). AF 95% confidence interval is 0.0322. There are 27 homozygotes in GnomAd4. There are 963 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1991 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.1329_1331delTGA	p.His443_Glu444delinsGln	disruptive_inframe_deletion	Exon 8 of 26	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.1329_1331delTGA	p.His443_Glu444delinsGln	disruptive_inframe_deletion	Exon 8 of 26	5	NM_032776.3	ENSP00000382204.2
JMJD1C	ENST00000542921.5	c.783_785delTGA	p.His261_Glu262delinsGln	disruptive_inframe_deletion	Exon 7 of 25	1		ENSP00000444682.1
JMJD1C	ENST00000402544.5	n.1301_1303delTGA		non_coding_transcript_exon_variant	Exon 5 of 22	1

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1987 AN: 152148 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0337

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00472

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00592 AC: 1472 AN: 248538 AF XY: 0.00532

Gnomad AFR exome AF: 0.0359

Gnomad AMR exome AF: 0.00730

Gnomad ASJ exome AF: 0.00249

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000372

Gnomad NFE exome AF: 0.00480

Gnomad OTH exome AF: 0.00613

GnomAD4 exome AF: 0.00518 AC: 7574 AN: 1461742 Hom.: 57 AF XY: 0.00495 AC XY: 3599 AN XY: 727178

African (AFR) AF: 0.0326 AC: 1090 AN: 33476

American (AMR) AF: 0.00787 AC: 352 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00264 AC: 69 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00231 AC: 199 AN: 86252

European-Finnish (FIN) AF: 0.000244 AC: 13 AN: 53358

Middle Eastern (MID) AF: 0.00780 AC: 45 AN: 5766

European-Non Finnish (NFE) AF: 0.00483 AC: 5376 AN: 1111960

Other (OTH) AF: 0.00712 AC: 430 AN: 60392

GnomAD4 genome AF: 0.0131 AC: 1991 AN: 152266 Hom.: 27 Cov.: 32 AF XY: 0.0129 AC XY: 963 AN XY: 74462

African (AFR) AF: 0.0337 AC: 1398 AN: 41528

American (AMR) AF: 0.0141 AC: 216 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4824

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00472 AC: 321 AN: 68026

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.00692 Hom.: 4

Bravo AF: 0.0143

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00551

EpiControl AF: 0.00605

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early myoclonic encephalopathy Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=179/21	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: rs141981100; hg19: chr10-64974595;