17-40861710-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BS1_Supporting
The NM_000223.4(KRT12):c.1436A>G(p.Asn479Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000446 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
KRT12
NM_000223.4 missense
NM_000223.4 missense
Scores
1
4
9
Clinical Significance
Conservation
PhyloP100: 7.01
Genes affected
KRT12 (HGNC:6414): (keratin 12) KRT12 encodes the type I intermediate filament chain keratin 12, expressed in corneal epithelia. Mutations in this gene lead to Meesmann corneal dystrophy. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3030172).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000472 (69/1461652) while in subpopulation NFE AF= 0.0000603 (67/1111826). AF 95% confidence interval is 0.0000481. There are 0 homozygotes in gnomad4_exome. There are 32 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT12 | NM_000223.4 | c.1436A>G | p.Asn479Ser | missense_variant | 8/8 | ENST00000251643.5 | |
LOC105371777 | XR_934754.3 | n.63+10850T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT12 | ENST00000251643.5 | c.1436A>G | p.Asn479Ser | missense_variant | 8/8 | 1 | NM_000223.4 | P1 | |
ENST00000579136.1 | n.62-1376T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152242Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
3
AN:
152242
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250596Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135582
GnomAD3 exomes
AF:
AC:
2
AN:
250596
Hom.:
AF XY:
AC XY:
1
AN XY:
135582
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000472 AC: 69AN: 1461652Hom.: 0 Cov.: 29 AF XY: 0.0000440 AC XY: 32AN XY: 727150
GnomAD4 exome
AF:
AC:
69
AN:
1461652
Hom.:
Cov.:
29
AF XY:
AC XY:
32
AN XY:
727150
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74384
GnomAD4 genome
?
AF:
AC:
3
AN:
152242
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74384
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
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 submitter | clinical testing | Ambry Genetics | Oct 26, 2022 | The c.1436A>G (p.N479S) alteration is located in exon 8 (coding exon 8) of the KRT12 gene. This alteration results from a A to G substitution at nucleotide position 1436, causing the asparagine (N) at amino acid position 479 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D
PrimateAI
Benign
T
Polyphen
P;P
Vest4
0.22
MVP
0.79
MPC
0.0016
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at