chr17-40863564-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_000223.4(KRT12):c.1016A>T(p.Gln339Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
KRT12
NM_000223.4 missense
NM_000223.4 missense
Scores
2
9
3
Clinical Significance
Conservation
PhyloP100: 4.16
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.83
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT12 | NM_000223.4 | c.1016A>T | p.Gln339Leu | missense_variant | 5/8 | ENST00000251643.5 | |
LOC105371777 | XR_934754.3 | n.63+12704T>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT12 | ENST00000251643.5 | c.1016A>T | p.Gln339Leu | missense_variant | 5/8 | 1 | NM_000223.4 | P1 | |
KRT12 | ENST00000648535.1 | n.167A>T | non_coding_transcript_exon_variant | 1/2 | |||||
KRT12 | ENST00000650597.1 | n.487A>T | non_coding_transcript_exon_variant | 5/6 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251476Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135912
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461892Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9AN XY: 727248
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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.1016A>T (p.Q339L) alteration is located in exon 5 (coding exon 5) of the KRT12 gene. This alteration results from a A to T substitution at nucleotide position 1016, causing the glutamine (Q) at amino acid position 339 to be replaced by a leucine (L). 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
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D
PrimateAI
Benign
T
Polyphen
D;D
Vest4
0.45
MutPred
Gain of catalytic residue at Q339 (P = 0.0053);Gain of catalytic residue at Q339 (P = 0.0053);
MVP
0.92
MPC
1.9
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at