10-59245444-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_032439.4(PHYHIPL):c.984C>T(p.Val328=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,614,120 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (11 hom.)
• Consequence: PHYHIPL NM_032439.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.506

Genes affected

PHYHIPL (HGNC:29378): (phytanoyl-CoA 2-hydroxylase interacting protein like) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 10-59245444-C-T is Benign according to our data. Variant chr10-59245444-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640482.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.506 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHYHIPL	NM_032439.4	c.984C>T	p.Val328=	synonymous_variant	5/5	ENST00000373880.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHYHIPL	ENST00000373880.9	c.984C>T	p.Val328=	synonymous_variant	5/5	1	NM_032439.4	P1
PHYHIPL	ENST00000373878.3	c.906C>T	p.Val302=	synonymous_variant	5/5	1
PHYHIPL	ENST00000486074.2	c.*925C>T		3_prime_UTR_variant, NMD_transcript_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 277 AN: 152144 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00222

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00226 AC: 566 AN: 250758 Hom.: 2 AF XY: 0.00227 AC XY: 307 AN XY: 135484

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.0206

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.00251

Gnomad OTH exome AF: 0.00360

GnomAD4 exome AF: 0.00245 AC: 3588 AN: 1461858 Hom.: 11 Cov.: 30 AF XY: 0.00242 AC XY: 1761 AN XY: 727228

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.0213

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.000393

Gnomad4 NFE exome AF: 0.00245

Gnomad4 OTH exome AF: 0.00361

GnomAD4 genome AF: 0.00182 AC: 277 AN: 152262 Hom.: 1 Cov.: 31 AF XY: 0.00177 AC XY: 132 AN XY: 74438

Gnomad4 AFR AF: 0.000577

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00222

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00355 Hom.: 0

Bravo AF: 0.00176

EpiCase AF: 0.00289

EpiControl AF: 0.00237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

PHYHIPL: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	6.8
Dann	Benign	0.70

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: rs138490289; hg19: chr10-61005204;