7-143139176-C-G

Variant names:

• chr7-143139176-C-G
• NM_002652.3:c.303C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002652.3(PIP):​c.303C>G​(p.Asp101Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIP NM_002652.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.164

Genes affected

PIP (HGNC:8993): (prolactin induced protein) Enables IgG binding activity; aspartic-type endopeptidase activity; and identical protein binding activity. Involved in several processes, including detection of chemical stimulus involved in sensory perception of bitter taste; negative regulation of T cell apoptotic process; and proteolysis. Located in extracellular space and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP	NM_002652.3	c.303C>G	p.Asp101Glu	missense_variant	Exon 3 of 4	ENST00000291009.4	NP_002643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP	ENST00000291009.4	c.303C>G	p.Asp101Glu	missense_variant	Exon 3 of 4	1	NM_002652.3	ENSP00000291009.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.303C>G (p.D101E) alteration is located in exon 3 (coding exon 3) of the PIP gene. This alteration results from a C to G substitution at nucleotide position 303, causing the aspartic acid (D) at amino acid position 101 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Uncertain	0.97
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0018	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.12
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.23	T
Polyphen		0.98	D
Vest4		0.27
MutPred		0.84		Loss of ubiquitination at K96 (P = 0.1166);
MVP		0.18
MPC		0.10
ClinPred		0.71	D
GERP RS		-1.8
Varity_R		0.24
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-142836269;