rs139722368

Variant names:

• chr10-63208190-ACTAAAC-A
• rs139722368
• NM_032776.3:c.3473_3478delGTTTAG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_032776.3(JMJD1C):​c.3473_3478delGTTTAG​(p.Gly1158_Leu1159del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0352 in 1,613,900 control chromosomes in the GnomAD database, including 2,327 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (277 hom., cov: 32)
  • Exomes 𝑓: 0.035 (2050 hom.)
• Consequence: JMJD1C NM_032776.3 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 4.51
• Publications: 8 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 -8 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_032776.3.
• BP6: Variant 10-63208190-ACTAAAC-A is Benign according to our data. Variant chr10-63208190-ACTAAAC-A is described in ClinVar as Benign. ClinVar VariationId is 529718.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 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.3473_3478delGTTTAG	p.Gly1158_Leu1159del	disruptive_inframe_deletion	Exon 10 of 26	NP_116165.1
	JMJD1C	NM_001322252.2		c.3359_3364delGTTTAG	p.Gly1120_Leu1121del	disruptive_inframe_deletion	Exon 9 of 25	NP_001309181.1
	JMJD1C	NM_001282948.2		c.2927_2932delGTTTAG	p.Gly976_Leu977del	disruptive_inframe_deletion	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.3473_3478delGTTTAG	p.Gly1158_Leu1159del	disruptive_inframe_deletion	Exon 10 of 26	ENSP00000382204.2
	JMJD1C	ENST00000542921.5	TSL:1	c.2927_2932delGTTTAG	p.Gly976_Leu977del	disruptive_inframe_deletion	Exon 9 of 25	ENSP00000444682.1
	JMJD1C	ENST00000402544.5	TSL:1	n.3445_3450delGTTTAG		non_coding_transcript_exon	Exon 7 of 22

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5305 AN: 152184 Hom.: 275 Cov.: 32

Gnomad AFR AF: 0.00917

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.0213

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0267

GnomAD2 exomes AF: 0.0533 AC: 13273 AN: 248954 AF XY: 0.0482

Gnomad AFR exome AF: 0.00898

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.269

Gnomad FIN exome AF: 0.0322

Gnomad NFE exome AF: 0.0247

Gnomad OTH exome AF: 0.0393

GnomAD4 exome AF: 0.0353 AC: 51559 AN: 1461598 Hom.: 2050 AF XY: 0.0340 AC XY: 24705 AN XY: 727110

African (AFR) AF: 0.00636 AC: 213 AN: 33474

American (AMR) AF: 0.112 AC: 4999 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 241 AN: 26132

East Asian (EAS) AF: 0.227 AC: 8997 AN: 39692

South Asian (SAS) AF: 0.0167 AC: 1443 AN: 86254

European-Finnish (FIN) AF: 0.0326 AC: 1742 AN: 53414

Middle Eastern (MID) AF: 0.00572 AC: 33 AN: 5766

European-Non Finnish (NFE) AF: 0.0282 AC: 31355 AN: 1111764

Other (OTH) AF: 0.0420 AC: 2536 AN: 60380

GnomAD4 genome AF: 0.0349 AC: 5308 AN: 152302 Hom.: 277 Cov.: 32 AF XY: 0.0373 AC XY: 2781 AN XY: 74480

African (AFR) AF: 0.00914 AC: 380 AN: 41584

American (AMR) AF: 0.0894 AC: 1367 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00979 AC: 34 AN: 3472

East Asian (EAS) AF: 0.261 AC: 1347 AN: 5162

South Asian (SAS) AF: 0.0215 AC: 104 AN: 4832

European-Finnish (FIN) AF: 0.0317 AC: 337 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0246 AC: 1670 AN: 68022

Other (OTH) AF: 0.0284 AC: 60 AN: 2116

Alfa AF: 0.0239 Hom.: 22

Bravo AF: 0.0395

Asia WGS AF: 0.120 AC: 415 AN: 3478

EpiCase AF: 0.0213

EpiControl AF: 0.0219

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Early myoclonic encephalopathy (1)
-	-	1	JMJD1C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5
Mutation Taster		=180/20	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs139722368; hg19: chr10-64967950; COSMIC: COSV59513271; COSMIC: COSV59513271;