rs3839912

Variant names:

• chr10-13278111-GTT-G
• rs3839912
• NM_006214.4:c.*188_*189delAA

Your query was ambiguous. Multiple possible variants found:

• chr10-13278111-GTT-G
• chr10-13278111-GTT-GT
• chr10-13278111-GTT-GTTT
• chr10-13278111-GTT-GTTTT
• chr10-13278111-GTT-GTTTTT
• chr10-13278111-GTT-GTTTTTTTT

Variant summary

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

The NM_006214.4(PHYH):​c.*188_*189delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 531,838 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: PHYH NM_006214.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

Genes affected

PHYH (HGNC:8940): (phytanoyl-CoA 2-hydroxylase) This gene is a member of the PhyH family and encodes a peroxisomal protein that is involved in the alpha-oxidation of 3-methyl branched fatty acids. Specifically, this protein converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA. Mutations in this gene have been associated with Refsum disease (RD) and deficient protein activity has been associated with Zellweger syndrome and rhizomelic chondrodysplasia punctata. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

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
PHYH	NM_006214.4	c.*188_*189delAA		3_prime_UTR_variant	Exon 9 of 9	ENST00000263038.9	NP_006205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHYH	ENST00000263038	c.*188_*189delAA		3_prime_UTR_variant	Exon 9 of 9	1	NM_006214.4	ENSP00000263038.4
PHYH	ENST00000396920	c.*188_*189delAA		3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000380126.3
PHYH	ENST00000396913	c.*188_*189delAA		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000380121.2

Frequencies

GnomAD3 genomes AF: 0.000206 AC: 31 AN: 150748 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000366

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000665

Gnomad ASJ AF: 0.00376

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000378 AC: 144 AN: 380974 Hom.: 0 AF XY: 0.000422 AC XY: 86 AN XY: 203610

Gnomad4 AFR exome AF: 0.000494

Gnomad4 AMR exome AF: 0.0000576

Gnomad4 ASJ exome AF: 0.00716

Gnomad4 EAS exome AF: 0.0000395

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000781

Gnomad4 NFE exome AF: 0.000168

Gnomad4 OTH exome AF: 0.000374

GnomAD4 genome AF: 0.000205 AC: 31 AN: 150864 Hom.: 0 Cov.: 0 AF XY: 0.000231 AC XY: 17 AN XY: 73612

Gnomad4 AFR AF: 0.000365

Gnomad4 AMR AF: 0.0000664

Gnomad4 ASJ AF: 0.00376

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs3839912; hg19: chr10-13320111;