14-59501263-T-C

Position:

• chr14-59501263-T-C

Variant summary

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

The NM_016475.5(JKAMP):​c.713T>C​(p.Ile238Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: JKAMP NM_016475.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

Genes affected

JKAMP (HGNC:20184): (JNK1/MAPK8 associated membrane protein) Enables ubiquitin protein ligase binding activity. Involved in ubiquitin-dependent ERAD pathway. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

L3HYPDH (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JKAMP	NM_016475.5	c.713T>C	p.Ile238Thr	missense_variant	6/7	ENST00000616435.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JKAMP	ENST00000616435.5	c.713T>C	p.Ile238Thr	missense_variant	6/7	5	NM_016475.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.713T>C (p.I238T) alteration is located in exon 6 (coding exon 6) of the JKAMP gene. This alteration results from a T to C substitution at nucleotide position 713, causing the isoleucine (I) at amino acid position 238 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.52	D;D;D;D;D
MetaSVM	Benign	-0.80	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.75	N;N;N;N;N
REVEL	Uncertain	0.37
Sift	Benign	0.062	T;T;T;T;D
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.59	P;.;P;P;.
Vest4		0.64
MVP		0.55
MPC		0.62
ClinPred		0.82	D
GERP RS		5.8
Varity_R		0.13
gMVP		0.44

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: chr14-59967981;