chr10-63209240-T-TAACAA

Position:

• chr10-63209240-T-TAACAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_032776.3(JMJD1C):​c.2695-6_2695-5insTTGTT variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.316

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.2695-6_2695-5insTTGTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.2695-6_2695-5insTTGTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_032776.3	ENSP00000382204
JMJD1C	ENST00000542921.5	c.2149-6_2149-5insTTGTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000444682	P1
JMJD1C	ENST00000402544.5	n.2667-6_2667-5insTTGTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1

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

GnomAD3 exomes AF: 0.00504 AC: 1158 AN: 229796 Hom.: 28 AF XY: 0.00408 AC XY: 510 AN XY: 125058

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 SAS exome AF: 0.0000751

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

Gnomad4 AFR exome AF: 0.0724

Gnomad4 AMR exome AF: 0.00380

Gnomad4 ASJ exome AF: 0.000358

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000111

Gnomad4 FIN exome AF: 0.0000378

Gnomad4 NFE exome AF: 0.000268

Gnomad4 OTH exome AF: 0.00500

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

Gnomad4 AFR AF: 0.0728

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0190

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early myoclonic encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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: rs60227922; hg19: chr10-64969000;