14-59504321-T-G

Variant names:

• chr14-59504321-T-G
• rs7560
• NM_016475.5:c.*249T>G

Variant summary

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

The NM_016475.5(JKAMP):​c.*249T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 461,498 control chromosomes in the GnomAD database, including 16,811 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 (5707 hom., cov: 32)
  • Exomes 𝑓: 0.26 (11104 hom.)
• Consequence: JKAMP NM_016475.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 15 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:):

CCDC175 (HGNC:19847): (coiled-coil domain containing 175)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• 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.*249T>G		3_prime_UTR	Exon 7 of 7	NP_057559.2
	JKAMP	NM_001284201.2		c.*249T>G		3_prime_UTR	Exon 7 of 7	NP_001271130.1	G3V2M4
	JKAMP	NM_001284202.2		c.*249T>G		3_prime_UTR	Exon 8 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.*249T>G		3_prime_UTR	Exon 7 of 7	ENSP00000479775.2	Q9P055-4
	JKAMP	ENST00000356057.9	TSL:1	c.*249T>G		3_prime_UTR	Exon 8 of 8	ENSP00000348351.5	Q9P055-5
	JKAMP	ENST00000425728.6	TSL:1	c.*249T>G		3_prime_UTR	Exon 7 of 7	ENSP00000389699.2	Q9P055-3

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40437 AN: 151980 Hom.: 5696 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: 0.125

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.259 AC: 79996 AN: 309398 Hom.: 11104 Cov.: 0 AF XY: 0.266 AC XY: 42856 AN XY: 161096

African (AFR) AF: 0.318 AC: 2908 AN: 9158

American (AMR) AF: 0.335 AC: 3723 AN: 11122

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 2921 AN: 10440

East Asian (EAS) AF: 0.191 AC: 4320 AN: 22590

South Asian (SAS) AF: 0.425 AC: 10325 AN: 24304

European-Finnish (FIN) AF: 0.133 AC: 2538 AN: 19052

Middle Eastern (MID) AF: 0.351 AC: 510 AN: 1454

European-Non Finnish (NFE) AF: 0.248 AC: 47781 AN: 192318

Other (OTH) AF: 0.262 AC: 4970 AN: 18960

GnomAD4 genome AF: 0.266 AC: 40498 AN: 152100 Hom.: 5707 Cov.: 32 AF XY: 0.264 AC XY: 19644 AN XY: 74342

African (AFR) AF: 0.316 AC: 13119 AN: 41502

American (AMR) AF: 0.317 AC: 4844 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 924 AN: 3464

East Asian (EAS) AF: 0.181 AC: 938 AN: 5178

South Asian (SAS) AF: 0.400 AC: 1917 AN: 4796

European-Finnish (FIN) AF: 0.125 AC: 1324 AN: 10606

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

European-Non Finnish (NFE) AF: 0.244 AC: 16588 AN: 67972

Other (OTH) AF: 0.266 AC: 560 AN: 2104

Alfa AF: 0.258 Hom.: 16131

Bravo AF: 0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.76
PhyloP100		-0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7560; hg19: chr14-59971039; COSMIC: COSV105038643; COSMIC: COSV105038643;