NM_001375567.1:c.176A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BS1

The NM_001375567.1(FOCAD):​c.176A>T​(p.Asn59Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N59S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

FOCAD
NM_001375567.1 missense

Scores

5
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.42

Publications

0 publications found
Variant links:
Genes affected
FOCAD (HGNC:23377): (focadhesin) Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]
FOCAD Gene-Disease associations (from GenCC):
  • liver disease, severe congenital
    Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000041 (6/1461832) while in subpopulation EAS AF = 0.000151 (6/39694). AF 95% confidence interval is 0.0000651. There are 0 homozygotes in GnomAdExome4. There are 4 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOCADNM_001375567.1 linkc.176A>T p.Asn59Ile missense_variant Exon 4 of 44 ENST00000338382.11 NP_001362496.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOCADENST00000338382.11 linkc.176A>T p.Asn59Ile missense_variant Exon 4 of 44 5 NM_001375567.1 ENSP00000344307.6 Q5VW36
FOCADENST00000380249.5 linkc.176A>T p.Asn59Ile missense_variant Exon 6 of 46 1 ENSP00000369599.1 Q5VW36

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461832
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727212
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33476
American (AMR)
AF:
0.00
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.000151
AC:
6
AN:
39694
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111970
Other (OTH)
AF:
0.00
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.517
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.065
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
19
DANN
Uncertain
0.99
Eigen
Benign
-0.13
Eigen_PC
Benign
-0.14
FATHMM_MKL
Benign
0.62
D
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.69
D;D
MetaSVM
Benign
-1.1
T
PhyloP100
2.4
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-4.0
D;D
REVEL
Benign
0.12
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.0090
D;D
Vest4
0.85
MutPred
0.45
Loss of catalytic residue at N59 (P = 0.0173);Loss of catalytic residue at N59 (P = 0.0173);
MVP
0.26
MPC
0.013
ClinPred
0.94
D
GERP RS
3.1
gMVP
0.49
Mutation Taster
=84/16
polymorphism

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

Other links and lift over

dbSNP: rs764916026; hg19: chr9-20720422; API