9-20720423-A-G

Variant summary

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

The NM_001375567.1(FOCAD):ā€‹c.176A>Gā€‹(p.Asn59Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,920 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 31)
Exomes š‘“: 0.000021 ( 0 hom. )

Consequence

FOCAD
NM_001375567.1 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42
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 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=0.12335417).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FOCADNM_001375567.1 linkuse as main transcriptc.176A>G p.Asn59Ser missense_variant 4/44 ENST00000338382.11 NP_001362496.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FOCADENST00000338382.11 linkuse as main transcriptc.176A>G p.Asn59Ser missense_variant 4/445 NM_001375567.1 ENSP00000344307 P1
FOCADENST00000380249.5 linkuse as main transcriptc.176A>G p.Asn59Ser missense_variant 6/461 ENSP00000369599 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152088
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251376
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1461832
Hom.:
0
Cov.:
32
AF XY:
0.0000206
AC XY:
15
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152088
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 15, 2023The c.176A>G (p.N59S) alteration is located in exon 6 (coding exon 3) of the FOCAD gene. This alteration results from a A to G substitution at nucleotide position 176, causing the asparagine (N) at amino acid position 59 to be replaced by a serine (S). 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
0.066
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
13
DANN
Benign
0.93
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.56
D
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.023
Sift
Benign
0.21
T;T
Sift4G
Benign
0.47
T;T
Vest4
0.35
MVP
0.24
MPC
0.0063
ClinPred
0.070
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
gMVP
0.18

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: rs764916026; hg19: chr9-20720422; API