chr10-63465476-G-C

Variant names:

• chr10-63465476-G-C
• rs768541846
• NM_032776.3:c.168+19C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032776.3(JMJD1C):​c.168+19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,431,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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+19C>G		intron	N/A	NP_116165.1	Q15652-1
	JMJD1C	NM_001322252.2		c.168+19C>G		intron	N/A	NP_001309181.1
	JMJD1C	NM_001318154.2		c.-379+56262C>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+19C>G		intron	N/A	ENSP00000382204.2	Q15652-1
	JMJD1C-AS1	ENST00000609436.1	TSL:6	n.248G>C		non_coding_transcript_exon	Exon 1 of 1
	JMJD1C	ENST00000633035.1	TSL:3	n.113+56262C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1431996 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 710436

African (AFR) AF: 0.00 AC: 0 AN: 33090

American (AMR) AF: 0.0000233 AC: 1 AN: 42998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24866

East Asian (EAS) AF: 0.00 AC: 0 AN: 39084

South Asian (SAS) AF: 0.00 AC: 0 AN: 83116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4974

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100502

Other (OTH) AF: 0.00 AC: 0 AN: 59188

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-0.12
PromoterAI		-0.022	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs768541846; hg19: chr10-65225236;