NM_012417.4:c.-292C>G

Variant names:

• chr17-67377863-C-G
• rs8866
• NM_012417.4:c.-292C>G

Variant summary

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

The NM_012417.4(PITPNC1):​c.-292C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 362,564 control chromosomes in the GnomAD database, including 20,455 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 0.27 (6956 hom., cov: 32)
  • Exomes 𝑓: 0.35 (13499 hom.)
• Consequence: PITPNC1 NM_012417.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 8 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]

ENSG00000297739 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012417.4. 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
	PITPNC1	NM_012417.4	MANE Select	c.-292C>G		5_prime_UTR	Exon 1 of 9	NP_036549.2
	PITPNC1	NM_181671.3		c.-292C>G		5_prime_UTR	Exon 1 of 10	NP_858057.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITPNC1	ENST00000581322.6	TSL:1 MANE Select	c.-292C>G		5_prime_UTR	Exon 1 of 9	ENSP00000464006.1
	PITPNC1	ENST00000580974.6	TSL:1	c.-292C>G		5_prime_UTR	Exon 1 of 10	ENSP00000463626.1
	ENSG00000297739	ENST00000750645.1		n.43G>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41112 AN: 152044 Hom.: 6959 Cov.: 32

Gnomad AFR AF: 0.0728

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.347 AC: 72961 AN: 210402 Hom.: 13499 Cov.: 0 AF XY: 0.346 AC XY: 36973 AN XY: 106968

African (AFR) AF: 0.0718 AC: 395 AN: 5498

American (AMR) AF: 0.273 AC: 1488 AN: 5448

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 1701 AN: 7364

East Asian (EAS) AF: 0.360 AC: 6184 AN: 17200

South Asian (SAS) AF: 0.196 AC: 1218 AN: 6200

European-Finnish (FIN) AF: 0.373 AC: 6831 AN: 18296

Middle Eastern (MID) AF: 0.167 AC: 182 AN: 1092

European-Non Finnish (NFE) AF: 0.374 AC: 50636 AN: 135378

Other (OTH) AF: 0.311 AC: 4326 AN: 13926

GnomAD4 genome AF: 0.270 AC: 41114 AN: 152162 Hom.: 6956 Cov.: 32 AF XY: 0.269 AC XY: 20010 AN XY: 74398

African (AFR) AF: 0.0727 AC: 3021 AN: 41564

American (AMR) AF: 0.260 AC: 3969 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 802 AN: 3470

East Asian (EAS) AF: 0.323 AC: 1667 AN: 5160

South Asian (SAS) AF: 0.219 AC: 1057 AN: 4826

European-Finnish (FIN) AF: 0.368 AC: 3899 AN: 10594

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25786 AN: 67938

Other (OTH) AF: 0.265 AC: 560 AN: 2114

Alfa AF: 0.228 Hom.: 674

Bravo AF: 0.255

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.9
DANN	Benign	0.82
PhyloP100		-0.089
PromoterAI		-0.21	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8866; hg19: chr17-65373979;