rs1190574141

Variant names:

• chr7-154954414-T-A
• NM_007349.4:c.2662A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-154954414-T-A
• chr7-154954414-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007349.4(PAXIP1):​c.2662A>T​(p.Ile888Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I888V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PAXIP1 NM_007349.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19821602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAXIP1	NM_007349.4	c.2662A>T	p.Ile888Phe	missense_variant	Exon 16 of 21	ENST00000404141.6	NP_031375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAXIP1	ENST00000404141.6	c.2662A>T	p.Ile888Phe	missense_variant	Exon 16 of 21	5	NM_007349.4	ENSP00000384048.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1391362 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 687428

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: 0.0000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.75
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.86	.;D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.35	N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.22
Sift	Benign	0.83	T;T
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.0040	B;B
Vest4		0.35
MutPred		0.46		Gain of ubiquitination at K885 (P = 0.1504);Gain of ubiquitination at K885 (P = 0.1504);
MVP		0.64
MPC		1.3
ClinPred		0.31	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.26
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr7-154746124;