rs751340

Positions:

• chr9-128927082-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001100876.2(PHYHD1):​c.78G>A​(p.Ala26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,613,836 control chromosomes in the GnomAD database, including 121,089 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 0.39 (11847 hom., cov: 31)
  • Exomes 𝑓: 0.38 (109242 hom.)
• Consequence: PHYHD1 NM_001100876.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.65

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-3.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHYHD1	NM_001100876.2	c.78G>A	p.Ala26=	synonymous_variant	4/13	ENST00000372592.8
PHYHD1	NM_174933.4	c.78G>A	p.Ala26=	synonymous_variant	4/12
PHYHD1	NM_001100877.1	c.78G>A	p.Ala26=	synonymous_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHYHD1	ENST00000372592.8	c.78G>A	p.Ala26=	synonymous_variant	4/13	2	NM_001100876.2	P1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59484 AN: 151908 Hom.: 11819 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.397

GnomAD3 exomes AF: 0.378 AC: 95050 AN: 251478 Hom.: 18538 AF XY: 0.374 AC XY: 50820 AN XY: 135912

Gnomad AFR exome AF: 0.420

Gnomad AMR exome AF: 0.449

Gnomad ASJ exome AF: 0.346

Gnomad EAS exome AF: 0.207

Gnomad SAS exome AF: 0.341

Gnomad FIN exome AF: 0.371

Gnomad NFE exome AF: 0.392

Gnomad OTH exome AF: 0.385

GnomAD4 exome AF: 0.384 AC: 560913 AN: 1461810 Hom.: 109242 Cov.: 54 AF XY: 0.382 AC XY: 277865 AN XY: 727214

Gnomad4 AFR exome AF: 0.433

Gnomad4 AMR exome AF: 0.447

Gnomad4 ASJ exome AF: 0.340

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.339

Gnomad4 FIN exome AF: 0.372

Gnomad4 NFE exome AF: 0.392

Gnomad4 OTH exome AF: 0.374

GnomAD4 genome AF: 0.392 AC: 59568 AN: 152026 Hom.: 11847 Cov.: 31 AF XY: 0.391 AC XY: 29051 AN XY: 74294

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.395

Alfa AF: 0.392 Hom.: 11193

Bravo AF: 0.398

Asia WGS AF: 0.280 AC: 977 AN: 3478

EpiCase AF: 0.391

EpiControl AF: 0.384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.72
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs751340; hg19: chr9-131689361; COSMIC: COSV58279867;