NM_032776.3:c.1392G>A

Variant names:

• chr10-63214775-C-T
• rs142118527
• NM_032776.3:c.1392G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_032776.3(JMJD1C):​c.1392G>A​(p.Ser464Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00493 in 1,613,484 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (30 hom.)
• Consequence: JMJD1C NM_032776.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0520
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-63214775-C-T is Benign according to our data. Variant chr10-63214775-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 460217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.052 with no splicing effect.
• BS2: High AC in GnomAd4 at 492 AD gene.

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.1392G>A	p.Ser464Ser	synonymous	Exon 8 of 26	NP_116165.1
	JMJD1C	NM_001322252.2		c.1278G>A	p.Ser426Ser	synonymous	Exon 7 of 25	NP_001309181.1
	JMJD1C	NM_001282948.2		c.846G>A	p.Ser282Ser	synonymous	Exon 7 of 25	NP_001269877.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.1392G>A	p.Ser464Ser	synonymous	Exon 8 of 26	ENSP00000382204.2
	JMJD1C	ENST00000542921.5	TSL:1	c.846G>A	p.Ser282Ser	synonymous	Exon 7 of 25	ENSP00000444682.1
	JMJD1C	ENST00000402544.5	TSL:1	n.1364G>A		non_coding_transcript_exon	Exon 5 of 22

Frequencies

GnomAD3 genomes AF: 0.00324 AC: 492 AN: 152076 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00556

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00307 AC: 765 AN: 248822 AF XY: 0.00319

Gnomad AFR exome AF: 0.00110

Gnomad AMR exome AF: 0.00151

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00195

Gnomad NFE exome AF: 0.00517

Gnomad OTH exome AF: 0.00447

GnomAD4 exome AF: 0.00511 AC: 7469 AN: 1461290 Hom.: 30 Cov.: 32 AF XY: 0.00507 AC XY: 3683 AN XY: 726992

African (AFR) AF: 0.000807 AC: 27 AN: 33476

American (AMR) AF: 0.00183 AC: 82 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000498 AC: 13 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00135 AC: 116 AN: 86240

European-Finnish (FIN) AF: 0.00246 AC: 131 AN: 53308

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5764

European-Non Finnish (NFE) AF: 0.00610 AC: 6781 AN: 1111582

Other (OTH) AF: 0.00517 AC: 312 AN: 60384

GnomAD4 genome AF: 0.00323 AC: 492 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.00296 AC XY: 220 AN XY: 74404

African (AFR) AF: 0.00106 AC: 44 AN: 41508

American (AMR) AF: 0.00301 AC: 46 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4814

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10592

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00556 AC: 378 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00419 Hom.: 1

Bravo AF: 0.00318

EpiCase AF: 0.00562

EpiControl AF: 0.00450

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Early myoclonic encephalopathy (1)
-	-	1	JMJD1C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.1
DANN	Benign	0.53
PhyloP100		0.052
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs142118527; hg19: chr10-64974535; COSMIC: COSV67867169; COSMIC: COSV67867169;