chr7-154968556-T-C

Variant names:

• chr7-154968556-T-C
• NM_007349.4:c.1645A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007349.4(PAXIP1):​c.1645A>G​(p.Met549Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PAXIP1 NM_007349.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0550
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034750372).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007349.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAXIP1	NM_007349.4	MANE Select	c.1645A>G	p.Met549Val	missense	Exon 7 of 21	NP_031375.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAXIP1	ENST00000404141.6	TSL:5 MANE Select	c.1645A>G	p.Met549Val	missense	Exon 7 of 21	ENSP00000384048.1	Q6ZW49-6
	PAXIP1	ENST00000919354.1		c.1423A>G	p.Met475Val	missense	Exon 4 of 18	ENSP00000589413.1
	PAXIP1	ENST00000457196.5	TSL:5	n.*1364A>G		non_coding_transcript_exon	Exon 8 of 22	ENSP00000392011.1	F8WC23

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 575320 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 309734

African (AFR) AF: 0.00 AC: 0 AN: 15990

American (AMR) AF: 0.00 AC: 0 AN: 34650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20060

East Asian (EAS) AF: 0.00 AC: 0 AN: 32088

South Asian (SAS) AF: 0.00 AC: 0 AN: 62750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3834

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 326998

Other (OTH) AF: 0.00 AC: 0 AN: 30954

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.9
DANN	Benign	0.30
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.055
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.033
Sift	Benign	0.13	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.20		Gain of MoRF binding (P = 0.1086)
MVP		0.17
MPC		0.15
ClinPred		0.077	T
GERP RS		-0.59
Varity_R		0.054
gMVP		0.16
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr7-154760266;