17-40863800-C-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_000223.4(KRT12):c.872G>T(p.Gly291Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,612,348 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
KRT12
NM_000223.4 missense
NM_000223.4 missense
Scores
3
7
4
Clinical Significance
Conservation
PhyloP100: 3.70
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 Likely_benign. Variant got -3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.798
BS2
?
High AC in GnomAdExome at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT12 | NM_000223.4 | c.872G>T | p.Gly291Val | missense_variant | 4/8 | ENST00000251643.5 | |
LOC105371777 | XR_934754.3 | n.63+12940C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT12 | ENST00000251643.5 | c.872G>T | p.Gly291Val | missense_variant | 4/8 | 1 | NM_000223.4 | P1 | |
KRT12 | ENST00000648126.1 | n.588G>T | non_coding_transcript_exon_variant | 2/2 | |||||
KRT12 | ENST00000650597.1 | n.343G>T | non_coding_transcript_exon_variant | 4/6 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152156Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250736Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135662
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GnomAD4 exome AF: 0.0000219 AC: 32AN: 1460192Hom.: 0 Cov.: 34 AF XY: 0.0000207 AC XY: 15AN XY: 726374
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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 | May 25, 2022 | The c.872G>T (p.G291V) alteration is located in exon 4 (coding exon 4) of the KRT12 gene. This alteration results from a G to T substitution at nucleotide position 872, causing the glycine (G) at amino acid position 291 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Pathogenic
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
0.55
MutPred
Loss of disorder (P = 0.0924);Loss of disorder (P = 0.0924);
MVP
0.86
MPC
0.74
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