rs10995485

Positions:

• chr10-63267098-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032776.3(JMJD1C):​c.334-2334C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 152,176 control chromosomes in the GnomAD database, including 33 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 0.016 (33 hom., cov: 32)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0162 (2471/152176) while in subpopulation NFE AF= 0.0246 (1670/67974). AF 95% confidence interval is 0.0236. There are 33 homozygotes in gnomad4. There are 1176 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2471 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.334-2334C>G		intron_variant		ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.334-2334C>G		intron_variant		5	NM_032776.3	ENSP00000382204

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2472 AN: 152058 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00369

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0306

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0129

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

GnomAD4 genome AF: 0.0162 AC: 2471 AN: 152176 Hom.: 33 Cov.: 32 AF XY: 0.0158 AC XY: 1176 AN XY: 74410

Gnomad4 AFR AF: 0.00368

Gnomad4 AMR AF: 0.0104

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.0306

Gnomad4 NFE AF: 0.0246

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0190 Hom.: 2

Bravo AF: 0.0142

Asia WGS AF: 0.00173 AC: 6 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.46
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs10995485; hg19: chr10-65026858;