11-12496553-G-C

Position:

• chr11-12496553-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018222.5(PARVA):​c.496G>C​(p.Glu166Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PARVA NM_018222.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.58

Genes affected

PARVA (HGNC:14652): (parvin alpha) This gene encodes a member of the parvin family of actin-binding proteins. Parvins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. The encoded protein is part of the integrin-linked kinase signaling complex and plays a role in cell adhesion, motility and survival. [provided by RefSeq, Dec 2010]

PARVA (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28799784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARVA	NM_018222.5	c.496G>C	p.Glu166Gln	missense_variant	5/13	ENST00000334956.15	NP_060692.3
PARVA	XM_005253015.4	c.364G>C	p.Glu122Gln	missense_variant	5/13		XP_005253072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARVA	ENST00000334956.15	c.496G>C	p.Glu166Gln	missense_variant	5/13	1	NM_018222.5	ENSP00000334008.9
PARVA	ENST00000528916.1	c.388G>C	p.Glu130Gln	missense_variant	5/8	5		ENSP00000435860.1
PARVA	ENST00000533345.5	n.473G>C		non_coding_transcript_exon_variant	5/8	5
PARVA	ENST00000533392.1	n.169G>C		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Jan 23, 2023

The c.616G>C (p.E206Q) alteration is located in exon 5 (coding exon 5) of the PARVA gene. This alteration results from a G to C substitution at nucleotide position 616, causing the glutamic acid (E) at amino acid position 206 to be replaced by a glutamine (Q). 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	Benign	0.12
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;.;.
Eigen	Benign	-0.014
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	D;.;D
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Uncertain	0.39	D
MutationAssessor	Benign	0.28	N;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.26	.;.;N
REVEL	Uncertain	0.33
Sift	Benign	0.46	.;.;T
Sift4G	Benign	0.47	.;.;T
Polyphen		0.019	B;.;.
MutPred		0.21		Gain of MoRF binding (P = 0.0162);.;.;
MVP		0.78
MPC		0.35
ClinPred		0.83	D
GERP RS		4.7
Varity_R		0.11
gMVP		0.24

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-12518100;