NM_032776.3:c.168+11C>G

Variant names:

• chr10-63465484-G-C
• rs1061259
• NM_032776.3:c.168+11C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032776.3(JMJD1C):​c.168+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,589,650 control chromosomes in the GnomAD database, including 484,136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (36092 hom., cov: 34)
  • Exomes 𝑓: 0.78 (448044 hom.)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.149
• Publications: 13 publications found

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]

JMJD1C-AS1 (HGNC:28222): (JMJD1C antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-63465484-G-C is Benign according to our data. Variant chr10-63465484-G-C is described in ClinVar as Benign. ClinVar VariationId is 1170745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032776.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	NM_032776.3	MANE Select	c.168+11C>G		intron	N/A	NP_116165.1	Q15652-1
	JMJD1C	NM_001322252.2		c.168+11C>G		intron	N/A	NP_001309181.1
	JMJD1C	NM_001318154.2		c.-379+56254C>G		intron	N/A	NP_001305083.1	Q15652-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.168+11C>G		intron	N/A	ENSP00000382204.2	Q15652-1
	JMJD1C-AS1	ENST00000609436.1	TSL:6	n.256G>C		non_coding_transcript_exon	Exon 1 of 1
	JMJD1C	ENST00000633035.1	TSL:3	n.113+56254C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100534 AN: 152112 Hom.: 36119 Cov.: 34

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.659

GnomAD2 exomes AF: 0.718 AC: 154868 AN: 215544 AF XY: 0.736

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.522

Gnomad ASJ exome AF: 0.834

Gnomad EAS exome AF: 0.687

Gnomad FIN exome AF: 0.825

Gnomad NFE exome AF: 0.805

Gnomad OTH exome AF: 0.752

GnomAD4 exome AF: 0.784 AC: 1127601 AN: 1437420 Hom.: 448044 Cov.: 39 AF XY: 0.786 AC XY: 560743 AN XY: 713444

African (AFR) AF: 0.356 AC: 11770 AN: 33098

American (AMR) AF: 0.532 AC: 23003 AN: 43222

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 21009 AN: 25312

East Asian (EAS) AF: 0.697 AC: 27271 AN: 39126

South Asian (SAS) AF: 0.752 AC: 63368 AN: 84290

European-Finnish (FIN) AF: 0.826 AC: 37243 AN: 45114

Middle Eastern (MID) AF: 0.707 AC: 3623 AN: 5126

European-Non Finnish (NFE) AF: 0.812 AC: 895187 AN: 1102732

Other (OTH) AF: 0.760 AC: 45127 AN: 59400

GnomAD4 genome AF: 0.660 AC: 100502 AN: 152230 Hom.: 36092 Cov.: 34 AF XY: 0.663 AC XY: 49370 AN XY: 74446

African (AFR) AF: 0.367 AC: 15243 AN: 41518

American (AMR) AF: 0.603 AC: 9226 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2906 AN: 3472

East Asian (EAS) AF: 0.695 AC: 3590 AN: 5162

South Asian (SAS) AF: 0.739 AC: 3565 AN: 4826

European-Finnish (FIN) AF: 0.825 AC: 8762 AN: 10624

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54889 AN: 68008

Other (OTH) AF: 0.658 AC: 1389 AN: 2112

Alfa AF: 0.720 Hom.: 5089

Bravo AF: 0.627

Asia WGS AF: 0.640 AC: 2225 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Early myoclonic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.5
DANN	Benign	0.71
PhyloP100		-0.15
PromoterAI		0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1061259; hg19: chr10-65225244;