chr9-100578424-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001018116.2(CAVIN4):​c.281G>A​(p.Arg94Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CAVIN4
NM_001018116.2 missense

Scores

5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05
Variant links:
Genes affected
CAVIN4 (HGNC:33742): (caveolae associated protein 4) This gene encodes a protein containing two coiled-coil regions. The encoded protein promotes Rho/ROCK (Rho-kinase) signaling in cardiac muscles cells, and may facilitate myofibrillar organization. [provided by RefSeq, Jun 2013]

Genome browser will be placed here

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=0.11495593).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CAVIN4NM_001018116.2 linkuse as main transcriptc.281G>A p.Arg94Gln missense_variant 1/2 ENST00000307584.6
CAVIN4XM_047423346.1 linkuse as main transcriptc.257G>A p.Arg86Gln missense_variant 2/3
CAVIN4XM_047423347.1 linkuse as main transcriptc.21+1469G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CAVIN4ENST00000307584.6 linkuse as main transcriptc.281G>A p.Arg94Gln missense_variant 1/21 NM_001018116.2 P1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152186
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250738
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135488
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461822
Hom.:
0
Cov.:
33
AF XY:
0.00000688
AC XY:
5
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152304
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000793
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsDec 16, 2023The c.281G>A (p.R94Q) alteration is located in exon 1 (coding exon 1) of the MURC gene. This alteration results from a G to A substitution at nucleotide position 281, causing the arginine (R) at amino acid position 94 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
0.070
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.26
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.92
T
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.25
T
PROVEAN
Uncertain
-3.6
D
REVEL
Benign
0.13
Sift
Uncertain
0.021
D
Sift4G
Uncertain
0.013
D
Polyphen
0.39
B
Vest4
0.14
MVP
0.29
MPC
0.044
ClinPred
0.23
T
GERP RS
1.2
Varity_R
0.29
gMVP
0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs191289133; hg19: chr9-103340706; COSMIC: COSV56867210; COSMIC: COSV56867210; API