rs10761770

Variant names:

• chr10-63465485-A-G
• rs10761770
• NM_032776.3:c.168+10T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-63465485-A-G
• chr10-63465485-A-C

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+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.993 in 1,592,154 control chromosomes in the GnomAD database, including 785,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70903 hom., cov: 34)
  • Exomes 𝑓: 1.0 (714554 hom.)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.20
• Publications: 12 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=-0.72).
• BP6: Variant 10-63465485-A-G is Benign according to our data. Variant chr10-63465485-A-G is described in ClinVar as Benign. ClinVar VariationId is 1164927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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+10T>C		intron	N/A	NP_116165.1	Q15652-1
	JMJD1C	NM_001322252.2		c.168+10T>C		intron	N/A	NP_001309181.1
	JMJD1C	NM_001318154.2		c.-379+56253T>C		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+10T>C		intron	N/A	ENSP00000382204.2	Q15652-1
	JMJD1C-AS1	ENST00000609436.1	TSL:6	n.257A>G		non_coding_transcript_exon	Exon 1 of 1
	JMJD1C	ENST00000633035.1	TSL:3	n.113+56253T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146628 AN: 152208 Hom.: 70852 Cov.: 34

Gnomad AFR AF: 0.874

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.968

GnomAD2 exomes AF: 0.990 AC: 216064 AN: 218256 AF XY: 0.992

Gnomad AFR exome AF: 0.862

Gnomad AMR exome AF: 0.993

Gnomad ASJ exome AF: 0.999

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.996 AC: 1434146 AN: 1439828 Hom.: 714554 Cov.: 41 AF XY: 0.997 AC XY: 712348 AN XY: 714838

African (AFR) AF: 0.866 AC: 28718 AN: 33144

American (AMR) AF: 0.993 AC: 43260 AN: 43578

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25396 AN: 25404

East Asian (EAS) AF: 1.00 AC: 39200 AN: 39200

South Asian (SAS) AF: 1.00 AC: 84502 AN: 84530

European-Finnish (FIN) AF: 1.00 AC: 45426 AN: 45430

Middle Eastern (MID) AF: 0.994 AC: 5123 AN: 5156

European-Non Finnish (NFE) AF: 1.00 AC: 1103547 AN: 1103888

Other (OTH) AF: 0.991 AC: 58974 AN: 59498

GnomAD4 genome AF: 0.963 AC: 146738 AN: 152326 Hom.: 70903 Cov.: 34 AF XY: 0.964 AC XY: 71816 AN XY: 74498

African (AFR) AF: 0.874 AC: 36320 AN: 41554

American (AMR) AF: 0.985 AC: 15078 AN: 15310

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5171 AN: 5172

South Asian (SAS) AF: 0.999 AC: 4827 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67990 AN: 68036

Other (OTH) AF: 0.969 AC: 2050 AN: 2116

Alfa AF: 0.987 Hom.: 90707

Bravo AF: 0.958

Asia WGS AF: 0.992 AC: 3450 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	-0.72
CADD	Benign	12
DANN	Benign	0.70
PhyloP100		1.2
PromoterAI		0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10761770; hg19: chr10-65225245;