rs117647164

Variant names:

• chr10-63214257-T-C
• rs117647164
• NM_032776.3:c.1910A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032776.3(JMJD1C):​c.1910A>G​(p.Lys637Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000688 in 1,614,042 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (18 hom.)
• Consequence: JMJD1C NM_032776.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.02

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=0.0033361316).
• BP6: Variant 10-63214257-T-C is Benign according to our data. Variant chr10-63214257-T-C is described in ClinVar as [Benign]. Clinvar id is 529721.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-63214257-T-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00113 (172/152298) while in subpopulation EAS AF= 0.0327 (169/5172). AF 95% confidence interval is 0.0287. There are 4 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 172 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.1910A>G	p.Lys637Arg	missense_variant	Exon 8 of 26	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.1910A>G	p.Lys637Arg	missense_variant	Exon 8 of 26	5	NM_032776.3	ENSP00000382204.2
JMJD1C	ENST00000542921.5	c.1364A>G	p.Lys455Arg	missense_variant	Exon 7 of 25	1		ENSP00000444682.1
JMJD1C	ENST00000402544.5	n.1882A>G		non_coding_transcript_exon_variant	Exon 5 of 22	1

Frequencies

GnomAD3 genomes AF: 0.00113 AC: 172 AN: 152180 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00246 AC: 613 AN: 249194 Hom.: 23 AF XY: 0.00224 AC XY: 303 AN XY: 135184

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0336

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.000642 AC: 939 AN: 1461744 Hom.: 18 Cov.: 33 AF XY: 0.000637 AC XY: 463 AN XY: 727178

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0224

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.000563

GnomAD4 genome AF: 0.00113 AC: 172 AN: 152298 Hom.: 4 Cov.: 32 AF XY: 0.00140 AC XY: 104 AN XY: 74474

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0327

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00121 Hom.: 3

Bravo AF: 0.00128

ExAC AF: 0.00241 AC: 291

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early myoclonic encephalopathy Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	.;T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T;T;T
MetaRNN	Benign	0.0033	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.0	.;M;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.0	.;N;N
REVEL	Benign	0.095
Sift	Pathogenic	0.0	.;D;D
Sift4G	Benign	0.22	.;T;T
Polyphen		1.0	.;D;.
Vest4		0.47, 0.49
MVP		0.85
MPC		0.37
ClinPred		0.14	T
GERP RS		5.0
Varity_R		0.30
gMVP		0.28

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: rs117647164; hg19: chr10-64974017;