rs777145719

Variant names:

• chr6-10697331-C-G
• rs777145719
• NM_017906.3:c.92C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-10697331-C-G
• chr6-10697331-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017906.3(PAK1IP1):​c.92C>G​(p.Thr31Ser) 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. 17/22 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. T31I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PAK1IP1 NM_017906.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

Genes affected

PAK1IP1 (HGNC:20882): (PAK1 interacting protein 1) Involved in regulation of signal transduction by p53 class mediator and ribosomal large subunit biogenesis. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09030485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAK1IP1	NM_017906.3	c.92C>G	p.Thr31Ser	missense_variant	Exon 2 of 10	ENST00000379568.4	NP_060376.2
PAK1IP1	XM_011514721.1	c.158C>G	p.Thr53Ser	missense_variant	Exon 3 of 11		XP_011513023.1
PAK1IP1	XM_005249204.3	c.95C>G	p.Thr32Ser	missense_variant	Exon 2 of 10		XP_005249261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK1IP1	ENST00000379568.4	c.92C>G	p.Thr31Ser	missense_variant	Exon 2 of 10	1	NM_017906.3	ENSP00000368887.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.2
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.082
Sift	Benign	0.35	T
Sift4G	Benign	0.45	T
Polyphen		0.021	B
Vest4		0.21
MutPred		0.32		Gain of disorder (P = 0.0769);
MVP		0.36
MPC		0.13
ClinPred		0.13	T
GERP RS		5.2
Varity_R		0.054
gMVP		0.23
Mutation Taster		=86/14	polymorphism

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: rs777145719; hg19: chr6-10697564;