NM_032776.3:c.4201T>A

Variant names:

• chr10-63207468-A-T
• NM_032776.3:c.4201T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032776.3(JMJD1C):​c.4201T>A​(p.Ser1401Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: JMJD1C NM_032776.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17953637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.4201T>A	p.Ser1401Thr	missense_variant	Exon 10 of 26	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.4201T>A	p.Ser1401Thr	missense_variant	Exon 10 of 26	5	NM_032776.3	ENSP00000382204.2
JMJD1C	ENST00000542921.5	c.3655T>A	p.Ser1219Thr	missense_variant	Exon 9 of 25	1		ENSP00000444682.1
JMJD1C	ENST00000402544.5	n.4173T>A		non_coding_transcript_exon_variant	Exon 7 of 22	1
JMJD1C	ENST00000327520.7	c.256T>A	p.Ser86Thr	missense_variant	Exon 1 of 12	2		ENSP00000335929.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461874 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.027	.;T;.
Eigen	Benign	-0.093
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	.;M;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	.;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.0010	.;D;D
Sift4G	Uncertain	0.032	.;D;D
Polyphen		0.92	.;P;.
Vest4		0.33, 0.26
MutPred		0.11		.;Loss of glycosylation at S1401 (P = 0.0471);.;
MVP		0.37
MPC		0.12
ClinPred		0.62	D
GERP RS		3.2
Varity_R		0.20
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-64967228;