7-154961554-C-T

Variant names:

• chr7-154961554-C-T
• rs779262380
• NM_007349.4:c.2222G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_007349.4(PAXIP1):​c.2222G>A​(p.Arg741His) variant causes a missense change. The variant allele was found at a frequency of 0.0000274 in 1,606,588 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: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: PAXIP1 NM_007349.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.402028).
• BS2: High AC in GnomAdExome4 at 41 AD gene.

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.2222G>A	p.Arg741His	missense	Exon 11 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.2222G>A	p.Arg741His	missense	Exon 11 of 21	ENSP00000384048.1	Q6ZW49-6
	PAXIP1	ENST00000919354.1		c.2000G>A	p.Arg667His	missense	Exon 8 of 18	ENSP00000589413.1
	PAXIP1	ENST00000457196.5	TSL:5	n.*1941G>A		non_coding_transcript_exon	Exon 12 of 22	ENSP00000392011.1	F8WC23

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152140 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000168 AC: 4 AN: 238094 AF XY: 0.0000155

Gnomad AFR exome AF: 0.000137

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000187

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000282 AC: 41 AN: 1454448 Hom.: 0 Cov.: 30 AF XY: 0.0000263 AC XY: 19 AN XY: 722784

African (AFR) AF: 0.0000299 AC: 1 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 43876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25936

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 84836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000343 AC: 38 AN: 1107958

Other (OTH) AF: 0.0000166 AC: 1 AN: 60122

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152140 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74318

African (AFR) AF: 0.0000483 AC: 2 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000774 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000414 AC: 5

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	Uncertain	0.37
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	D
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	0.38	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.5
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.049	D
Polyphen		0.25	B
Vest4		0.43
MVP		0.77
MPC		1.0
ClinPred		0.81	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.72
Mutation Taster		=38/62	disease causing

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

Other links and lift over

dbSNP: rs779262380; hg19: chr7-154753264;