NM_012417.4:c.49-65156T>C

Variant names:

• chr17-67467646-T-C
• rs7217437
• NM_012417.4:c.49-65156T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012417.4(PITPNC1):​c.49-65156T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,934 control chromosomes in the GnomAD database, including 27,983 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 0.59 (27983 hom., cov: 31)
• Consequence: PITPNC1 NM_012417.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 4 publications found

Genes affected

PITPNC1 (HGNC:21045): (phosphatidylinositol transfer protein cytoplasmic 1) This gene encodes a member of the phosphatidylinositol transfer protein family. The encoded cytoplasmic protein plays a role in multiple processes including cell signaling and lipid metabolism by facilitating the transfer of phosphatidylinositol between membrane compartments. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 1. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNC1	NM_012417.4	c.49-65156T>C		intron_variant	Intron 1 of 8	ENST00000581322.6	NP_036549.2
PITPNC1	NM_181671.3	c.49-65156T>C		intron_variant	Intron 1 of 9		NP_858057.1
PITPNC1	XM_047435746.1	c.-21-65156T>C		intron_variant	Intron 1 of 8		XP_047291702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITPNC1	ENST00000581322.6	c.49-65156T>C		intron_variant	Intron 1 of 8	1	NM_012417.4	ENSP00000464006.1
PITPNC1	ENST00000580974.6	c.49-65156T>C		intron_variant	Intron 1 of 9	1		ENSP00000463626.1
PITPNC1	ENST00000584554.1	c.-22+7854T>C		intron_variant	Intron 2 of 5	5		ENSP00000464364.1
PITPNC1	ENST00000584471.5	c.-21-65156T>C		intron_variant	Intron 1 of 4	5		ENSP00000464584.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89281 AN: 151816 Hom.: 27920 Cov.: 31

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.575

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.588 AC: 89407 AN: 151934 Hom.: 27983 Cov.: 31 AF XY: 0.595 AC XY: 44192 AN XY: 74252

African (AFR) AF: 0.789 AC: 32728 AN: 41464

American (AMR) AF: 0.653 AC: 9974 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1789 AN: 3470

East Asian (EAS) AF: 0.705 AC: 3631 AN: 5152

South Asian (SAS) AF: 0.707 AC: 3403 AN: 4810

European-Finnish (FIN) AF: 0.492 AC: 5183 AN: 10526

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30822 AN: 67924

Other (OTH) AF: 0.578 AC: 1221 AN: 2112

Alfa AF: 0.510 Hom.: 44687

Bravo AF: 0.610

Asia WGS AF: 0.697 AC: 2423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.6
DANN	Benign	0.82
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs7217437; hg19: chr17-65463762;