9-128927081-C-A

Variant names:

• chr9-128927081-C-A
• NM_001100876.2:c.77C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001100876.2(PHYHD1):​c.77C>A​(p.Ala26Glu) 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 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. A26V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PHYHD1 NM_001100876.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06484142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHYHD1	NM_001100876.2	c.77C>A	p.Ala26Glu	missense_variant	Exon 4 of 13	ENST00000372592.8	NP_001094346.1
PHYHD1	NM_174933.4	c.77C>A	p.Ala26Glu	missense_variant	Exon 4 of 12		NP_777593.2
PHYHD1	NM_001100877.1	c.77C>A	p.Ala26Glu	missense_variant	Exon 2 of 10		NP_001094347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHYHD1	ENST00000372592.8	c.77C>A	p.Ala26Glu	missense_variant	Exon 4 of 13	2	NM_001100876.2	ENSP00000361673.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	1.3
DANN	Benign	0.91
DEOGEN2	Benign	0.17	T;T;.;T;.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.55	T;T;T;T;.;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.065	T;T;T;T;T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.83	L;.;L;.;L;.;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.080	N;N;N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.55	T;T;T;T;T;T;T
Sift4G	Benign	0.45	T;T;T;T;T;T;T
Polyphen		0.023	B;.;B;.;B;.;B
Vest4		0.20
MutPred		0.54		Gain of disorder (P = 0.0478);Gain of disorder (P = 0.0478);Gain of disorder (P = 0.0478);Gain of disorder (P = 0.0478);Gain of disorder (P = 0.0478);Gain of disorder (P = 0.0478);Gain of disorder (P = 0.0478);
MVP		0.23
MPC		0.19
ClinPred		0.10	T
GERP RS		1.7
Varity_R		0.16
gMVP		0.46

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-131689360;