rs149833441

chr10-63208491-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_032776.3(JMJD1C):c.3178A>G(p.Lys1060Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000442 in 1,614,058 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00055 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (5 hom.)
• Consequence: JMJD1C NM_032776.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.32

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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006677717).
• BP6: Variant 10-63208491-T-C is Benign according to our data. Variant chr10-63208491-T-C is described in ClinVar as [Benign]. Clinvar id is 460236.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 84 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD1C	NM_032776.3	c.3178A>G	p.Lys1060Glu	missense_variant	10/26	ENST00000399262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000399262.7	c.3178A>G	p.Lys1060Glu	missense_variant	10/26	5	NM_032776.3
JMJD1C	ENST00000542921.5	c.2632A>G	p.Lys878Glu	missense_variant	9/25	1		P1
JMJD1C	ENST00000402544.5	n.3150A>G		non_coding_transcript_exon_variant	7/22	1

Frequencies

GnomAD3 genomes AF: 0.000552 AC: 84 AN: 152192 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00136 AC: 340 AN: 249230 Hom.: 3 AF XY: 0.00122 AC XY: 165 AN XY: 135196

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0187

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000430 AC: 629 AN: 1461748 Hom.: 5 Cov.: 33 AF XY: 0.000421 AC XY: 306 AN XY: 727162

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0149

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.000513

GnomAD4 genome AF: 0.000552 AC: 84 AN: 152310 Hom.: 1 Cov.: 32 AF XY: 0.000577 AC XY: 43 AN XY: 74490

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000912 Hom.: 2

Bravo AF: 0.000797

ExAC AF: 0.00130 AC: 157

Asia WGS AF: 0.00173 AC: 6 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

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.090
Cadd	Benign	23
Dann	Uncertain	1.0
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.93	D;D;D
MetaRNN	Benign	0.0067	T;T;T
MetaSVM	Benign	-0.80	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.51	T
Polyphen		0.87	.;P;.
Vest4		0.47, 0.53
MVP		0.58
MPC		0.33
ClinPred		0.084	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs149833441; hg19: chr10-64968251; COSMIC: COSV59513849; COSMIC: COSV59513849;