7-154968659-A-G

Position:

• chr7-154968659-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007349.4(PAXIP1):​c.1542T>C​(p.Leu514Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 716,086 control chromosomes in the GnomAD database, including 129,922 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 (26538 hom., cov: 31)
  • Exomes 𝑓: 0.60 (103384 hom.)
• Consequence: PAXIP1 NM_007349.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-0.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAXIP1	NM_007349.4	c.1542T>C	p.Leu514Leu	synonymous_variant	7/21	ENST00000404141.6	NP_031375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAXIP1	ENST00000404141.6	c.1542T>C	p.Leu514Leu	synonymous_variant	7/21	5	NM_007349.4	ENSP00000384048.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89513 AN: 151140 Hom.: 26508 Cov.: 31

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.651

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.615

GnomAD3 exomes AF: 0.624 AC: 96270 AN: 154284 Hom.: 30407 AF XY: 0.619 AC XY: 50468 AN XY: 81474

Gnomad AFR exome AF: 0.535

Gnomad AMR exome AF: 0.747

Gnomad ASJ exome AF: 0.647

Gnomad EAS exome AF: 0.592

Gnomad SAS exome AF: 0.606

Gnomad FIN exome AF: 0.644

Gnomad NFE exome AF: 0.589

Gnomad OTH exome AF: 0.631

GnomAD4 exome AF: 0.603 AC: 340652 AN: 564828 Hom.: 103384 Cov.: 2 AF XY: 0.601 AC XY: 183152 AN XY: 304776

Gnomad4 AFR exome AF: 0.537

Gnomad4 AMR exome AF: 0.742

Gnomad4 ASJ exome AF: 0.642

Gnomad4 EAS exome AF: 0.563

Gnomad4 SAS exome AF: 0.608

Gnomad4 FIN exome AF: 0.646

Gnomad4 NFE exome AF: 0.584

Gnomad4 OTH exome AF: 0.609

GnomAD4 genome AF: 0.592 AC: 89596 AN: 151258 Hom.: 26538 Cov.: 31 AF XY: 0.597 AC XY: 44154 AN XY: 73904

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.612

Alfa AF: 0.593 Hom.: 4808

Bravo AF: 0.593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.1
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs935037; hg19: chr7-154760369; COSMIC: COSV68184659; COSMIC: COSV68184659;