ENST00000373878.3:c.*2183A>C

Variant names:

• chr10-59247774-A-C
• rs1459996
• ENST00000373878.3:c.*2183A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000373878.3(PHYHIPL):​c.*2183A>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHYHIPL ENST00000373878.3 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 9 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000373878.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM13C	NM_198215.4	MANE Select	c.1635-37T>G		intron	N/A	NP_937858.2
	FAM13C	NM_001143773.1		c.1386-37T>G		intron	N/A	NP_001137245.1
	FAM13C	NM_001347840.2		c.1386-37T>G		intron	N/A	NP_001334769.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYHIPL	ENST00000373878.3	TSL:1	c.*2183A>C		splice_region	Exon 5 of 5	ENSP00000362985.3
	PHYHIPL	ENST00000373878.3	TSL:1	c.*2183A>C		3_prime_UTR	Exon 5 of 5	ENSP00000362985.3
	FAM13C	ENST00000618804.5	TSL:1 MANE Select	c.1635-37T>G		intron	N/A	ENSP00000481854.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1435964 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 713174

African (AFR) AF: 0.00 AC: 0 AN: 32472

American (AMR) AF: 0.00 AC: 0 AN: 42692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25770

East Asian (EAS) AF: 0.00 AC: 0 AN: 39160

South Asian (SAS) AF: 0.00 AC: 0 AN: 83282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095752

Other (OTH) AF: 0.00 AC: 0 AN: 59462

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.8
DANN	Benign	0.70
PhyloP100		1.6

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

Other links and lift over

dbSNP: rs1459996; hg19: chr10-61007534;