GeneBe

9-20717796-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001375567.1(FOCAD):​c.60T>G​(p.Ala20Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A20A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FOCAD
NM_001375567.1 splice_region, synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.308

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 -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP7
Synonymous conserved (PhyloP=0.308 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOCADNM_001375567.1 linkc.60T>G p.Ala20Ala splice_region_variant, synonymous_variant Exon 3 of 44 ENST00000338382.11 NP_001362496.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOCADENST00000338382.11 linkc.60T>G p.Ala20Ala splice_region_variant, synonymous_variant Exon 3 of 44 5 NM_001375567.1 ENSP00000344307.6 Q5VW36
FOCADENST00000380249.5 linkc.60T>G p.Ala20Ala splice_region_variant, synonymous_variant Exon 5 of 46 1 ENSP00000369599.1 Q5VW36

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458624
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
725778
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33408
American (AMR)
AF:
0.00
AC:
0
AN:
44666
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26080
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39540
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86152
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52292
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
9.01e-7
AC:
1
AN:
1110466
Other (OTH)
AF:
0.00
AC:
0
AN:
60264
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
CADD
Benign
13
DANN
Benign
0.85
PhyloP100
0.31

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: rs901054327; hg19: chr9-20717795; API