Menu
GeneBe

9-20740318-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001375567.1(FOCAD):c.370A>G(p.Ile124Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,606,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

FOCAD
NM_001375567.1 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.262
Variant links:
Genes affected
FOCAD (HGNC:23377): (focadhesin) Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.013756841).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOCADNM_001375567.1 linkuse as main transcriptc.370A>G p.Ile124Val missense_variant 5/44 ENST00000338382.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOCADENST00000338382.11 linkuse as main transcriptc.370A>G p.Ile124Val missense_variant 5/445 NM_001375567.1 P1
FOCADENST00000380249.5 linkuse as main transcriptc.370A>G p.Ile124Val missense_variant 7/461 P1
FOCADENST00000604103.1 linkuse as main transcriptn.165A>G non_coding_transcript_exon_variant 2/54
FOCADENST00000605031.5 linkuse as main transcriptn.146A>G non_coding_transcript_exon_variant 2/54

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
152032
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00220
Gnomad AMR
AF:
0.00
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:
0.000338
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000998
AC:
25
AN:
250430
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135342
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000221
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000137
AC:
200
AN:
1454682
Hom.:
0
Cov.:
27
AF XY:
0.000133
AC XY:
96
AN XY:
724134
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000174
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152146
Hom.:
0
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000338
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000248
Hom.:
0
Bravo
AF:
0.000151
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000140
AC:
17

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeJan 03, 2024This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 124 of the FOCAD protein (p.Ile124Val). This variant is present in population databases (rs139972395, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with FOCAD-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.68
Cadd
Benign
5.1
Dann
Benign
0.23
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.032
N
M_CAP
Benign
0.0043
T
MetaRNN
Benign
0.014
T;T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.090
N;N
REVEL
Benign
0.031
Sift
Benign
0.46
T;T
Sift4G
Benign
0.94
T;T
Vest4
0.18
MVP
0.27
MPC
0.0061
ClinPred
0.24
T
GERP RS
1.4
gMVP
0.15

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: rs139972395; hg19: chr9-20740317; API