NM_001318154.2:c.-379+6571T>C

Variant names:

• chr10-63515167-A-G
• rs10761779
• NM_001318154.2:c.-379+6571T>C

Variant summary

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

The NM_001318154.2(JMJD1C):​c.-379+6571T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,852 control chromosomes in the GnomAD database, including 14,174 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 0.42 (14174 hom., cov: 31)
• Consequence: JMJD1C NM_001318154.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 51 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318154.2. 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_001318154.2		c.-379+6571T>C		intron	N/A	NP_001305083.1	Q15652-3
	JMJD1C	NM_001322258.2		c.-384+6571T>C		intron	N/A	NP_001309187.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000633035.1	TSL:3	n.113+6571T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63921 AN: 151734 Hom.: 14188 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.421 AC: 63896 AN: 151852 Hom.: 14174 Cov.: 31 AF XY: 0.421 AC XY: 31214 AN XY: 74198

African (AFR) AF: 0.301 AC: 12464 AN: 41408

American (AMR) AF: 0.342 AC: 5221 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2031 AN: 3464

East Asian (EAS) AF: 0.390 AC: 2006 AN: 5138

South Asian (SAS) AF: 0.533 AC: 2561 AN: 4808

European-Finnish (FIN) AF: 0.463 AC: 4873 AN: 10522

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.488 AC: 33138 AN: 67942

Other (OTH) AF: 0.426 AC: 897 AN: 2104

Alfa AF: 0.461 Hom.: 67125

Bravo AF: 0.398

Asia WGS AF: 0.434 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.54
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs10761779; hg19: chr10-65274927;