chr14-59504321-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016475.5(JKAMP):​c.*249T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 462,190 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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>A		3_prime_UTR	Exon 7 of 7	NP_057559.2
	JKAMP	NM_001284201.2		c.*249T>A		3_prime_UTR	Exon 7 of 7	NP_001271130.1	G3V2M4
	JKAMP	NM_001284202.2		c.*249T>A		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>A		3_prime_UTR	Exon 7 of 7	ENSP00000479775.2	Q9P055-4
	JKAMP	ENST00000356057.9	TSL:1	c.*249T>A		3_prime_UTR	Exon 8 of 8	ENSP00000348351.5	Q9P055-5
	JKAMP	ENST00000425728.6	TSL:1	c.*249T>A		3_prime_UTR	Exon 7 of 7	ENSP00000389699.2	Q9P055-3

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152036 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000129 AC: 4 AN: 310154 Hom.: 0 Cov.: 0 AF XY: 0.0000124 AC XY: 2 AN XY: 161476

African (AFR) AF: 0.000327 AC: 3 AN: 9184

American (AMR) AF: 0.00 AC: 0 AN: 11162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10472

East Asian (EAS) AF: 0.00 AC: 0 AN: 22628

South Asian (SAS) AF: 0.00 AC: 0 AN: 24374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1462

European-Non Finnish (NFE) AF: 0.00000519 AC: 1 AN: 192776

Other (OTH) AF: 0.00 AC: 0 AN: 19004

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152036 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74246

African (AFR) AF: 0.000193 AC: 8 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 16131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.6
DANN	Benign	0.80
PhyloP100		-0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;