7-154957286-T-A

Position:

• chr7-154957286-T-A

Variant summary

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

The NM_007349.4(PAXIP1):​c.2487A>T​(p.Arg829Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PAXIP1 NM_007349.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.09

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.2487A>T	p.Arg829Ser	missense_variant	14/21	ENST00000404141.6	NP_031375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAXIP1	ENST00000404141.6	c.2487A>T	p.Arg829Ser	missense_variant	14/21	5	NM_007349.4	ENSP00000384048.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1437120 Hom.: 0 Cov.: 25 AF XY: 0.00000140 AC XY: 1 AN XY: 715264

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.14e-7

Gnomad4 OTH exome AF: 0.00

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

Jun 16, 2024

The c.2487A>T (p.R829S) alteration is located in exon 14 (coding exon 14) of the PAXIP1 gene. This alteration results from a A to T substitution at nucleotide position 2487, causing the arginine (R) at amino acid position 829 to be replaced by a serine (S). 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	Uncertain	0.46
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	4.0
DANN	Benign	0.72
DEOGEN2	Benign	0.18	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.89	.;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.22
Sift	Benign	0.10	T;T
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.98	D;D
Vest4		0.38
MutPred		0.44		Gain of ubiquitination at K833 (P = 0.0408);Gain of ubiquitination at K833 (P = 0.0408);
MVP		0.41
MPC		0.92
ClinPred		0.53	D
GERP RS		-5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: 8

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: chr7-154748996;