5-178211964-T-G

Variant names:

• chr5-178211964-T-G
• NM_153373.4:c.1310A>C

Variant summary

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

The NM_153373.4(PHYKPL):​c.1310A>C​(p.Glu437Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E437V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PHYKPL NM_153373.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33

Genes affected

PHYKPL (HGNC:28249): (5-phosphohydroxy-L-lysine phospho-lyase) This is a nuclear gene encoding a mitochondrial enzyme that catalyzes the conversion of 5-phosphonooxy-L-lysine to ammonia, inorganic phosphate, and 2-aminoadipate semialdehyde. Mutations in this gene may cause phosphohydroxylysinuria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHYKPL	NM_153373.4	c.1310A>C	p.Glu437Ala	missense_variant	Exon 12 of 13	ENST00000308158.10	NP_699204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHYKPL	ENST00000308158.10	c.1310A>C	p.Glu437Ala	missense_variant	Exon 12 of 13	1	NM_153373.4	ENSP00000310978.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727234

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.032
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.63
Sift	Uncertain	0.028	D
Sift4G	Benign	0.10	T
Polyphen		0.077	B
Vest4		0.68
MutPred		0.38		Loss of disorder (P = 0.0576);
MVP		0.87
MPC		0.14
ClinPred		0.93	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-177638965;