10-63447988-A-G

Variant names:

• chr10-63447988-A-G
• rs10509187
• NM_032776.3:c.168+17507T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032776.3(JMJD1C):​c.168+17507T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 152,074 control chromosomes in the GnomAD database, including 266 homozygotes. 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: 𝑓 0.031 (266 hom., cov: 30)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 1 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 Gene-Disease associations (from GenCC):

• 22q11.2 deletion syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.168+17507T>C		intron_variant	Intron 1 of 25	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.168+17507T>C		intron_variant	Intron 1 of 25	5	NM_032776.3	ENSP00000382204.2
JMJD1C	ENST00000633035.1	n.114-67506T>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 4706 AN: 151956 Hom.: 264 Cov.: 30

Gnomad AFR AF: 0.00725

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.00578

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0273

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0310 AC: 4711 AN: 152074 Hom.: 266 Cov.: 30 AF XY: 0.0340 AC XY: 2526 AN XY: 74354

African (AFR) AF: 0.00723 AC: 300 AN: 41522

American (AMR) AF: 0.0849 AC: 1296 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00578 AC: 20 AN: 3460

East Asian (EAS) AF: 0.261 AC: 1352 AN: 5172

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4812

European-Finnish (FIN) AF: 0.0398 AC: 421 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0174 AC: 1184 AN: 67956

Other (OTH) AF: 0.0289 AC: 61 AN: 2110

Alfa AF: 0.00972 Hom.: 8

Bravo AF: 0.0346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.4
DANN	Benign	0.75
PhyloP100		1.6
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: rs10509187; hg19: chr10-65207748;