chr14-59495118-C-T

Variant names:

• chr14-59495118-C-T
• rs773352543
• NM_016475.5:c.352C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016475.5(JKAMP):​c.352C>T​(p.Arg118Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,012 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R118H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: JKAMP NM_016475.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67
• Publications: 1 publications found

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:20488): (trans-L-3-hydroxyproline dehydratase) The protein encoded by this gene is a dehydratase that converts trans-3-hydroxy-L-proline to delta(1)-pyrroline-2-carboxylate. This enzyme may function to degrade dietary proteins that contain trans-3-hydroxy-L-proline as well as other proteins such as collagen IV. The encoded protein can be converted to an epimerase by changing a threonine to a cysteine at a catalytic site. [provided by RefSeq, Sep 2016]

ENSG00000258782 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016475.5. 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
	JKAMP	NM_016475.5	MANE Select	c.352C>T	p.Arg118Cys	missense	Exon 4 of 7	NP_057559.2
	JKAMP	NM_001284201.2		c.394C>T	p.Arg132Cys	missense	Exon 4 of 7	NP_001271130.1	G3V2M4
	JKAMP	NM_001284202.2		c.376C>T	p.Arg126Cys	missense	Exon 5 of 8	NP_001271131.1	Q9P055-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JKAMP	ENST00000616435.5	TSL:5 MANE Select	c.352C>T	p.Arg118Cys	missense	Exon 4 of 7	ENSP00000479775.2	Q9P055-4
	JKAMP	ENST00000356057.9	TSL:1	c.376C>T	p.Arg126Cys	missense	Exon 5 of 8	ENSP00000348351.5	Q9P055-5
	JKAMP	ENST00000425728.6	TSL:1	c.334C>T	p.Arg112Cys	missense	Exon 4 of 7	ENSP00000389699.2	Q9P055-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249256 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461012 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726818

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111276

Other (OTH) AF: 0.00 AC: 0 AN: 60344

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000827 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	33
DANN	Uncertain	1.0
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0067	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.62	T
PhyloP100		4.7
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.56
Sift	Benign	0.11	T
Sift4G	Benign	0.16	T
Polyphen		0.99	D
Vest4		0.67
MVP		0.51
MPC		1.5
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.11
gMVP		0.76
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs773352543; hg19: chr14-59961836; COSMIC: COSV104370940;