11-12518475-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_018222.5(PARVA):c.1000A>T(p.Met334Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,812 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 0.00024 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
PARVA
NM_018222.5 missense
NM_018222.5 missense
Scores
3
6
7
Clinical Significance
Conservation
PhyloP100: 9.29
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21726158).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PARVA | NM_018222.5 | c.1000A>T | p.Met334Leu | missense_variant | 12/13 | ENST00000334956.15 | |
PARVA | XM_005253015.4 | c.868A>T | p.Met290Leu | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PARVA | ENST00000334956.15 | c.1000A>T | p.Met334Leu | missense_variant | 12/13 | 1 | NM_018222.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000237 AC: 36AN: 152166Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000442 AC: 11AN: 248888Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135044
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461528Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 727024
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GnomAD4 genome ? AF: 0.000236 AC: 36AN: 152284Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74474
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2022 | The c.1120A>T (p.M374L) alteration is located in exon 12 (coding exon 12) of the PARVA gene. This alteration results from a A to T substitution at nucleotide position 1120, causing the methionine (M) at amino acid position 374 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Benign
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
REVEL
Uncertain
Polyphen
D;.
MutPred
Loss of loop (P = 0.1242);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at