rs143894691

Variant names:

• chr10-63207718-A-G
• rs143894691
• NM_032776.3:c.3951T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-63207718-A-G
• chr10-63207718-A-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_032776.3(JMJD1C):​c.3951T>C​(p.Ser1317Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000997 in 1,614,182 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (9 hom.)
• Consequence: JMJD1C NM_032776.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.686
• Publications: 4 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.032).
• BP6: Variant 10-63207718-A-G is Benign according to our data. Variant chr10-63207718-A-G is described in ClinVar as Benign. ClinVar VariationId is 460242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.686 with no splicing effect.
• BS2: High AC in GnomAd4 at 93 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.3951T>C	p.Ser1317Ser	synonymous	Exon 10 of 26	NP_116165.1
	JMJD1C	NM_001322252.2		c.3837T>C	p.Ser1279Ser	synonymous	Exon 9 of 25	NP_001309181.1
	JMJD1C	NM_001282948.2		c.3405T>C	p.Ser1135Ser	synonymous	Exon 9 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.3951T>C	p.Ser1317Ser	synonymous	Exon 10 of 26	ENSP00000382204.2
	JMJD1C	ENST00000542921.5	TSL:1	c.3405T>C	p.Ser1135Ser	synonymous	Exon 9 of 25	ENSP00000444682.1
	JMJD1C	ENST00000402544.5	TSL:1	n.3923T>C		non_coding_transcript_exon	Exon 7 of 22

Frequencies

GnomAD3 genomes AF: 0.000618 AC: 94 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00123 AC: 307 AN: 249206 AF XY: 0.00141

Gnomad AFR exome AF: 0.000323

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.000558

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.00104 AC: 1516 AN: 1461854 Hom.: 9 Cov.: 34 AF XY: 0.00118 AC XY: 855 AN XY: 727224

African (AFR) AF: 0.000239 AC: 8 AN: 33480

American (AMR) AF: 0.00168 AC: 75 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000804 AC: 21 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00494 AC: 426 AN: 86254

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53412

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5766

European-Non Finnish (NFE) AF: 0.000825 AC: 917 AN: 1111990

Other (OTH) AF: 0.000960 AC: 58 AN: 60396

GnomAD4 genome AF: 0.000611 AC: 93 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.000738 AC XY: 55 AN XY: 74492

African (AFR) AF: 0.000168 AC: 7 AN: 41574

American (AMR) AF: 0.00137 AC: 21 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000457 Hom.: 0

Bravo AF: 0.000661

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.000356

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Early myoclonic encephalopathy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.65
PhyloP100		-0.69
PromoterAI		0.022	Neutral
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: rs143894691; hg19: chr10-64967478;