10-59247774-A-G

Position:

• chr10-59247774-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000373878.3(PHYHIPL):​c.*2183A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 1,585,548 control chromosomes in the GnomAD database, including 542,358 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.75 (45235 hom., cov: 32)
  • Exomes 𝑓: 0.83 (497123 hom.)
• Consequence: PHYHIPL ENST00000373878.3 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

Genes affected

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

FAM13C (HGNC:19371): (family with sequence similarity 13 member C)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM13C	NM_198215.4	c.1635-37T>C		intron_variant		ENST00000618804.5	NP_937858.2
PHYHIPL	NM_032439.4	c.*2183A>G		downstream_gene_variant		ENST00000373880.9	NP_115815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM13C	ENST00000618804.5	c.1635-37T>C		intron_variant		1	NM_198215.4	ENSP00000481854.1
PHYHIPL	ENST00000373880.9	c.*2183A>G		downstream_gene_variant		1	NM_032439.4	ENSP00000362987.4

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114657 AN: 151926 Hom.: 45227 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.789

GnomAD3 exomes AF: 0.820 AC: 197626 AN: 241036 Hom.: 82210 AF XY: 0.820 AC XY: 106799 AN XY: 130314

Gnomad AFR exome AF: 0.499

Gnomad AMR exome AF: 0.868

Gnomad ASJ exome AF: 0.827

Gnomad EAS exome AF: 0.913

Gnomad SAS exome AF: 0.720

Gnomad FIN exome AF: 0.895

Gnomad NFE exome AF: 0.846

Gnomad OTH exome AF: 0.832

GnomAD4 exome AF: 0.830 AC: 1189762 AN: 1433504 Hom.: 497123 Cov.: 26 AF XY: 0.828 AC XY: 589388 AN XY: 712000

Gnomad4 AFR exome AF: 0.490

Gnomad4 AMR exome AF: 0.869

Gnomad4 ASJ exome AF: 0.828

Gnomad4 EAS exome AF: 0.851

Gnomad4 SAS exome AF: 0.720

Gnomad4 FIN exome AF: 0.896

Gnomad4 NFE exome AF: 0.844

Gnomad4 OTH exome AF: 0.815

GnomAD4 genome AF: 0.754 AC: 114696 AN: 152044 Hom.: 45235 Cov.: 32 AF XY: 0.759 AC XY: 56443 AN XY: 74346

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.854

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.895

Gnomad4 NFE AF: 0.847

Gnomad4 OTH AF: 0.788

Alfa AF: 0.835 Hom.: 104205

Bravo AF: 0.741

Asia WGS AF: 0.776 AC: 2696 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.4
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1459996; hg19: chr10-61007534; COSMIC: COSV53253395; COSMIC: COSV53253395;