rs751340

Variant names:

• chr9-128927082-G-A
• rs751340
• NM_001100876.2:c.78G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001100876.2(PHYHD1):​c.78G>A​(p.Ala26Ala) 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
• Publications: 25 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: Benign. The variant received -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.

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.78G>A	p.Ala26Ala	synonymous	Exon 4 of 13	NP_001094346.1	Q5SRE7-1
	PHYHD1	NM_174933.4		c.78G>A	p.Ala26Ala	synonymous	Exon 4 of 12	NP_777593.2	Q5SRE7-3
	PHYHD1	NM_001100877.1		c.78G>A	p.Ala26Ala	synonymous	Exon 2 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.78G>A	p.Ala26Ala	synonymous	Exon 4 of 13	ENSP00000361673.3	Q5SRE7-1
	PHYHD1	ENST00000308941.9	TSL:1	c.78G>A	p.Ala26Ala	synonymous	Exon 4 of 12	ENSP00000309515.5	Q5SRE7-3
	PHYHD1	ENST00000421063.6	TSL:1	c.78G>A	p.Ala26Ala	synonymous	Exon 2 of 10	ENSP00000409928.2	Q5SRE7-2

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

GnomAD2 exomes AF: 0.378 AC: 95050 AN: 251478 AF XY: 0.374

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 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

African (AFR) AF: 0.433 AC: 14499 AN: 33478

American (AMR) AF: 0.447 AC: 19986 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 8896 AN: 26136

East Asian (EAS) AF: 0.198 AC: 7868 AN: 39696

South Asian (SAS) AF: 0.339 AC: 29272 AN: 86252

European-Finnish (FIN) AF: 0.372 AC: 19893 AN: 53416

Middle Eastern (MID) AF: 0.418 AC: 2412 AN: 5766

European-Non Finnish (NFE) AF: 0.392 AC: 435487 AN: 1111964

Other (OTH) AF: 0.374 AC: 22600 AN: 60380

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

African (AFR) AF: 0.419 AC: 17371 AN: 41480

American (AMR) AF: 0.432 AC: 6593 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1221 AN: 3472

East Asian (EAS) AF: 0.223 AC: 1149 AN: 5156

South Asian (SAS) AF: 0.327 AC: 1578 AN: 4824

European-Finnish (FIN) AF: 0.376 AC: 3977 AN: 10564

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26419 AN: 67960

Other (OTH) AF: 0.395 AC: 834 AN: 2110

Alfa AF: 0.394 Hom.: 13054

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.72
DANN	Benign	0.48
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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