rs139722368

chr10-63208190-ACTAAAC-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BA1

The NM_032776.3(JMJD1C):c.3473_3478del(p.Gly1158_Leu1159del) variant causes a 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 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.51

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 -14 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 id is 529718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD1C	NM_032776.3	c.3473_3478del	p.Gly1158_Leu1159del	inframe_deletion	10/26	ENST00000399262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000399262.7	c.3473_3478del	p.Gly1158_Leu1159del	inframe_deletion	10/26	5	NM_032776.3
JMJD1C	ENST00000542921.5	c.2927_2932del	p.Gly976_Leu977del	inframe_deletion	9/25	1		P1
JMJD1C	ENST00000402544.5	n.3445_3450del		non_coding_transcript_exon_variant	7/22	1

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

GnomAD3 exomes AF: 0.0533 AC: 13273 AN: 248954 Hom.: 1034 AF XY: 0.0482 AC XY: 6516 AN XY: 135062

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 SAS exome AF: 0.0162

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

Gnomad4 AFR exome AF: 0.00636

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.00922

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.0167

Gnomad4 FIN exome AF: 0.0326

Gnomad4 NFE exome AF: 0.0282

Gnomad4 OTH exome AF: 0.0420

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

Gnomad4 AFR AF: 0.00914

Gnomad4 AMR AF: 0.0894

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.0215

Gnomad4 FIN AF: 0.0317

Gnomad4 NFE AF: 0.0246

Gnomad4 OTH AF: 0.0284

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

JMJD1C-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Early myoclonic encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs139722368; hg19: chr10-64967950;