10-63168075-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_032776.3(JMJD1C):c.7593G>A(p.Glu2531=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000298 in 1,603,428 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (4 hom.)
• Consequence: JMJD1C NM_032776.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.73

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 10-63168075-C-T is Benign according to our data. Variant chr10-63168075-C-T is described in ClinVar as [Benign]. Clinvar id is 460279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.73 with no splicing effect.
• BS2: High AC in GnomAd at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD1C	NM_032776.3	c.7593G>A	p.Glu2531=	synonymous_variant	26/26	ENST00000399262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000399262.7	c.7593G>A	p.Glu2531=	synonymous_variant	26/26	5	NM_032776.3
JMJD1C	ENST00000542921.5	c.7047G>A	p.Glu2349=	synonymous_variant	25/25	1		P1
JMJD1C	ENST00000402544.5	n.7284G>A		non_coding_transcript_exon_variant	22/22	1
JMJD1C	ENST00000467356.5	n.451G>A		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.000408 AC: 62 AN: 152086 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00144 AC: 358 AN: 248668 Hom.: 4 AF XY: 0.00110 AC XY: 149 AN XY: 134964

Gnomad AFR exome AF: 0.000711

Gnomad AMR exome AF: 0.00983

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.000287 AC: 416 AN: 1451224 Hom.: 4 Cov.: 28 AF XY: 0.000230 AC XY: 166 AN XY: 722720

Gnomad4 AFR exome AF: 0.000270

Gnomad4 AMR exome AF: 0.00857

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000145

Gnomad4 OTH exome AF: 0.000133

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152204 Hom.: 1 Cov.: 32 AF XY: 0.000349 AC XY: 26 AN XY: 74416

Gnomad4 AFR AF: 0.000482

Gnomad4 AMR AF: 0.00262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000136 Hom.: 0

Bravo AF: 0.000892

Asia WGS AF: 0.000289 AC: 1 AN: 3476

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

Invitae

Dec 22, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	2.9
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs186321056; hg19: chr10-64927835;