10-63168063-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032776.3(JMJD1C):c.7605G>C(p.Glu2535Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,584,334 control chromosomes in the GnomAD database, including 173,701 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.43 (14532 hom., cov: 32)
  • Exomes 𝑓: 0.47 (159169 hom.)
• Consequence: JMJD1C NM_032776.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00500

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.

• BP4: Computational evidence support a benign effect (MetaRNN=2.9492378E-4).
• BP6: Variant 10-63168063-C-G is Benign according to our data. Variant chr10-63168063-C-G is described in ClinVar as [Benign]. Clinvar id is 1167960.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD1C	NM_032776.3	c.7605G>C	p.Glu2535Asp	missense_variant	26/26	ENST00000399262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000399262.7	c.7605G>C	p.Glu2535Asp	missense_variant	26/26	5	NM_032776.3
JMJD1C	ENST00000542921.5	c.7059G>C	p.Glu2353Asp	missense_variant	25/25	1		P1
JMJD1C	ENST00000402544.5	n.7296G>C		non_coding_transcript_exon_variant	22/22	1
JMJD1C	ENST00000467356.5	n.463G>C		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64991 AN: 151814 Hom.: 14546 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.427

GnomAD3 exomes AF: 0.438 AC: 108928 AN: 248440 Hom.: 25300 AF XY: 0.452 AC XY: 61012 AN XY: 134850

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.571

Gnomad EAS exome AF: 0.334

Gnomad SAS exome AF: 0.533

Gnomad FIN exome AF: 0.470

Gnomad NFE exome AF: 0.484

Gnomad OTH exome AF: 0.454

GnomAD4 exome AF: 0.467 AC: 668979 AN: 1432402 Hom.: 159169 Cov.: 27 AF XY: 0.472 AC XY: 337084 AN XY: 714480

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.572

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.533

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.474

Gnomad4 OTH exome AF: 0.456

GnomAD4 genome AF: 0.428 AC: 64963 AN: 151932 Hom.: 14532 Cov.: 32 AF XY: 0.428 AC XY: 31758 AN XY: 74254

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.425

Alfa AF: 0.479 Hom.: 13748

Bravo AF: 0.405

TwinsUK AF: 0.486 AC: 1803

ALSPAC AF: 0.475 AC: 1831

ESP6500AA AF: 0.340 AC: 1271

ESP6500EA AF: 0.478 AC: 3919

ExAC AF: 0.445 AC: 53808

Asia WGS AF: 0.418 AC: 1452 AN: 3476

EpiCase AF: 0.488

EpiControl AF: 0.480

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	10
Dann	Uncertain	1.0
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.66	T;T;T
MetaRNN	Benign	0.00029	T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	0.15	P;P;P;P
PrimateAI	Benign	0.42	T
Polyphen		0.35	.;B;.
Vest4		0.060, 0.16
MutPred		0.095		.;Loss of loop (P = 0.1258);.;
MPC		0.99
ClinPred		0.013	T
GERP RS		3.6
Varity_R		0.054
gMVP		0.16

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: rs1935; hg19: chr10-64927823; COSMIC: COSV67858085;