chr22-44151515-C-G

Position:

• chr22-44151515-C-G

Variant summary

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

The NM_013327.5(PARVB):​c.807C>G​(p.Asn269Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N269S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARVB NM_013327.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.734

Genes affected

PARVB (HGNC:14653): (parvin beta) This gene encodes a member of the parvin family of actin-binding proteins, which play a role in cytoskeleton organization and cell adhesion. These proteins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. This family member binds to alphaPIX and alpha-actinin, and it can inhibit the activity of integrin-linked kinase. This protein also functions in tumor suppression. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARVB	NM_013327.5	c.807C>G	p.Asn269Lys	missense_variant	10/13	ENST00000338758.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARVB	ENST00000338758.12	c.807C>G	p.Asn269Lys	missense_variant	10/13	1	NM_013327.5	P3
	ENST00000624919.1	n.12151C>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 01, 2022

The c.906C>G (p.N302K) alteration is located in exon 11 (coding exon 11) of the PARVB gene. This alteration results from a C to G substitution at nucleotide position 906, causing the asparagine (N) at amino acid position 302 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	.;D;.
Eigen	Benign	0.067
Eigen_PC	Benign	0.070
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.7	.;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.025	D;D;D
Sift4G	Benign	0.074	T;T;.
Polyphen		0.80	P;P;.
Vest4		0.81
MutPred		0.37		.;Gain of MoRF binding (P = 0.043);.;
MVP		0.59
MPC		0.50
ClinPred		0.96	D
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr22-44547395;