6-10702446-G-A

Variant names:

• chr6-10702446-G-A
• rs1360031821
• NM_017906.3:c.325G>A

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.325G>A​(p.Asp109Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. D109H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: PAK1IP1 NM_017906.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.27
• 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=0.2114565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAK1IP1	NM_017906.3	c.325G>A	p.Asp109Asn	missense_variant	Exon 3 of 10	ENST00000379568.4	NP_060376.2
PAK1IP1	XM_011514721.1	c.391G>A	p.Asp131Asn	missense_variant	Exon 4 of 11		XP_011513023.1
PAK1IP1	XM_005249204.3	c.328G>A	p.Asp110Asn	missense_variant	Exon 3 of 10		XP_005249261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK1IP1	ENST00000379568.4	c.325G>A	p.Asp109Asn	missense_variant	Exon 3 of 10	1	NM_017906.3	ENSP00000368887.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251466 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461746 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727184

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111880

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.075
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.87	L
PhyloP100		4.3
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.087
Sift	Benign	0.68	T
Sift4G	Benign	0.76	T
Polyphen		0.0050	B
Vest4		0.35
MutPred		0.68		Gain of methylation at K112 (P = 0.0646);
MVP		0.67
MPC		0.15
ClinPred		0.18	T
GERP RS		5.9
Varity_R		0.043
gMVP		0.42
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: rs1360031821; hg19: chr6-10702679;