9-128936468-G-T

Variant names:

• chr9-128936468-G-T
• rs200242321
• NM_001100876.2:c.337G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001100876.2(PHYHD1):​c.337G>T​(p.Val113Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V113I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PHYHD1 NM_001100876.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 0 publications found

Genes affected

PHYHD1 (HGNC:23396): (phytanoyl-CoA dioxygenase domain containing 1) Enables 2-oxoglutarate-dependent dioxygenase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100876.2. 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
	PHYHD1	NM_001100876.2	MANE Select	c.337G>T	p.Val113Phe	missense	Exon 7 of 13	NP_001094346.1	Q5SRE7-1
	PHYHD1	NM_174933.4		c.337G>T	p.Val113Phe	missense	Exon 7 of 12	NP_777593.2	Q5SRE7-3
	PHYHD1	NM_001100877.1		c.337G>T	p.Val113Phe	missense	Exon 5 of 10	NP_001094347.1	Q5SRE7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYHD1	ENST00000372592.8	TSL:2 MANE Select	c.337G>T	p.Val113Phe	missense	Exon 7 of 13	ENSP00000361673.3	Q5SRE7-1
	PHYHD1	ENST00000308941.9	TSL:1	c.337G>T	p.Val113Phe	missense	Exon 7 of 12	ENSP00000309515.5	Q5SRE7-3
	PHYHD1	ENST00000421063.6	TSL:1	c.337G>T	p.Val113Phe	missense	Exon 5 of 10	ENSP00000409928.2	Q5SRE7-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 248992 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	-0.071
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.60	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.4
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.017	D
Polyphen		0.82	P
Vest4		0.67
MutPred		0.48		Gain of loop (P = 0.069)
MVP		0.51
MPC		0.67
ClinPred		0.97	D
GERP RS		2.1
Varity_R		0.74
gMVP		0.73
Mutation Taster		=67/33	polymorphism

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: rs200242321; hg19: chr9-131698747;