NM_032776.3:c.2695-10_2695-6dupTTGTT

Variant names:

• chr10-63209240-T-TAACAA
• rs60227922
• NM_032776.3:c.2695-10_2695-6dupTTGTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_032776.3(JMJD1C):​c.2695-10_2695-6dupTTGTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.004 in 1,588,536 control chromosomes in the GnomAD database, including 205 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (115 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (90 hom.)
• Consequence: JMJD1C NM_032776.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.316
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 10-63209240-T-TAACAA is Benign according to our data. Variant chr10-63209240-T-TAACAA is described in ClinVar as Benign. ClinVar VariationId is 460233.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0706 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.2695-10_2695-6dupTTGTT		splice_region intron	N/A	NP_116165.1
	JMJD1C	NM_001322252.2		c.2581-10_2581-6dupTTGTT		splice_region intron	N/A	NP_001309181.1
	JMJD1C	NM_001282948.2		c.2149-10_2149-6dupTTGTT		splice_region intron	N/A	NP_001269877.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.2695-6_2695-5insTTGTT		splice_region intron	N/A	ENSP00000382204.2
	JMJD1C	ENST00000542921.5	TSL:1	c.2149-6_2149-5insTTGTT		splice_region intron	N/A	ENSP00000444682.1
	JMJD1C	ENST00000402544.5	TSL:1	n.2667-6_2667-5insTTGTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3250 AN: 151928 Hom.: 115 Cov.: 32

Gnomad AFR AF: 0.0729

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0192

GnomAD2 exomes AF: 0.00504 AC: 1158 AN: 229796 AF XY: 0.00408

Gnomad AFR exome AF: 0.0673

Gnomad AMR exome AF: 0.00346

Gnomad ASJ exome AF: 0.000773

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000429

Gnomad OTH exome AF: 0.00328

GnomAD4 exome AF: 0.00216 AC: 3096 AN: 1436490 Hom.: 90 Cov.: 31 AF XY: 0.00191 AC XY: 1365 AN XY: 714088

African (AFR) AF: 0.0724 AC: 2308 AN: 31858

American (AMR) AF: 0.00380 AC: 150 AN: 39500

Ashkenazi Jewish (ASJ) AF: 0.000358 AC: 9 AN: 25148

East Asian (EAS) AF: 0.00 AC: 0 AN: 39212

South Asian (SAS) AF: 0.000111 AC: 9 AN: 81228

European-Finnish (FIN) AF: 0.0000378 AC: 2 AN: 52922

Middle Eastern (MID) AF: 0.00478 AC: 27 AN: 5654

European-Non Finnish (NFE) AF: 0.000268 AC: 295 AN: 1101758

Other (OTH) AF: 0.00500 AC: 296 AN: 59210

GnomAD4 genome AF: 0.0214 AC: 3252 AN: 152046 Hom.: 115 Cov.: 32 AF XY: 0.0211 AC XY: 1565 AN XY: 74334

African (AFR) AF: 0.0728 AC: 3014 AN: 41420

American (AMR) AF: 0.0102 AC: 156 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68004

Other (OTH) AF: 0.0190 AC: 40 AN: 2110

Alfa AF: 0.00318 Hom.: 2

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Early myoclonic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.32
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs60227922; hg19: chr10-64969000;