14-59504056-G-C

Position:

• chr14-59504056-G-C

Variant summary

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

The NM_016475.5(JKAMP):​c.920G>C​(p.Gly307Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,458,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: JKAMP NM_016475.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.38

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21210846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JKAMP	NM_016475.5	c.920G>C	p.Gly307Ala	missense_variant	7/7	ENST00000616435.5	NP_057559.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JKAMP	ENST00000616435.5	c.920G>C	p.Gly307Ala	missense_variant	7/7	5	NM_016475.5	ENSP00000479775	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458428 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725748

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

May 08, 2023

The c.920G>C (p.G307A) alteration is located in exon 7 (coding exon 7) of the JKAMP gene. This alteration results from a G to C substitution at nucleotide position 920, causing the glycine (G) at amino acid position 307 to be replaced by an alanine (A). 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	Benign	0.25
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Benign	-0.016
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.23	N;N;N;N
REVEL	Uncertain	0.37
Sift	Benign	0.15	T;T;T;T
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.0080	B;.;B;B
Vest4		0.31
MVP		0.52
MPC		0.54
ClinPred		0.81	D
GERP RS		5.7
Varity_R		0.15
gMVP		0.76

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: chr14-59970774;