7-154954317-A-G

Position:

• chr7-154954317-A-G

Variant summary

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

The NM_007349.4(PAXIP1):​c.2759T>C​(p.Val920Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PAXIP1 NM_007349.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.19

Genes affected

PAXIP1 (HGNC:8624): (PAX interacting protein 1) This gene is a member of the paired box (PAX) gene family and encodes a nuclear protein with six BRCT (breast cancer carboxy-terminal) domains. This protein plays a critical role in maintaining genome stability, condensation of chromatin and progression through mitosis. [provided by RefSeq, Jul 2008]

PAXIP1 (HGNC:):

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/exons	MANE	Protein	UniProt
PAXIP1	NM_007349.4	c.2759T>C	p.Val920Ala	missense_variant	16/21	ENST00000404141.6	NP_031375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAXIP1	ENST00000404141.6	c.2759T>C	p.Val920Ala	missense_variant	16/21	5	NM_007349.4	ENSP00000384048.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.2759T>C (p.V920A) alteration is located in exon 16 (coding exon 16) of the PAXIP1 gene. This alteration results from a T to C substitution at nucleotide position 2759, causing the valine (V) at amino acid position 920 to be replaced by an alanine (A). 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	Benign	0.17
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	23
DANN	Benign	0.67
DEOGEN2	Benign	0.082	T;T
Eigen	Benign	-0.041
Eigen_PC	Benign	-0.0086
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.59
Sift	Benign	0.36	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.44	B;B
Vest4		0.67
MutPred		0.54		Gain of ubiquitination at K922 (P = 0.1047);Gain of ubiquitination at K922 (P = 0.1047);
MVP		0.95
MPC		0.98
ClinPred		0.59	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.080
gMVP		0.69

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: chr7-154746027; COSMIC: COSV68185407; COSMIC: COSV68185407;