14-59492132-C-T

Variant names:

• chr14-59492132-C-T
• rs2182836
• NM_016475.5:c.252-2886C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016475.5(JKAMP):​c.252-2886C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,744 control chromosomes in the GnomAD database, including 5,696 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5696 hom., cov: 32)
• Consequence: JKAMP NM_016475.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

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.252-2886C>T		intron	N/A	NP_057559.2
	JKAMP	NM_001284201.2		c.294-2886C>T		intron	N/A	NP_001271130.1
	JKAMP	NM_001284202.2		c.276-2886C>T		intron	N/A	NP_001271131.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JKAMP	ENST00000616435.5	TSL:5 MANE Select	c.252-2886C>T		intron	N/A	ENSP00000479775.2
	JKAMP	ENST00000356057.9	TSL:1	c.276-2886C>T		intron	N/A	ENSP00000348351.5
	JKAMP	ENST00000425728.6	TSL:1	c.234-2886C>T		intron	N/A	ENSP00000389699.2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40390 AN: 151626 Hom.: 5686 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.266

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.267 AC: 40450 AN: 151744 Hom.: 5696 Cov.: 32 AF XY: 0.265 AC XY: 19633 AN XY: 74136

African (AFR) AF: 0.317 AC: 13086 AN: 41340

American (AMR) AF: 0.318 AC: 4846 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3464

East Asian (EAS) AF: 0.181 AC: 932 AN: 5148

South Asian (SAS) AF: 0.400 AC: 1923 AN: 4806

European-Finnish (FIN) AF: 0.127 AC: 1328 AN: 10492

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16568 AN: 67920

Other (OTH) AF: 0.264 AC: 557 AN: 2106

Alfa AF: 0.248 Hom.: 1661

Bravo AF: 0.280

Asia WGS AF: 0.274 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.74
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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: rs2182836; hg19: chr14-59958850;