13-94443596-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_001922.5(DCT):c.1221G>A(p.Met407Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000157 in 1,461,656 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: not found (cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
DCT
NM_001922.5 missense
NM_001922.5 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 5.04
Genes affected
DCT (HGNC:2709): (dopachrome tautomerase) Predicted to enable dopachrome isomerase activity. Involved in response to blue light. Located in intracellular membrane-bounded organelle and plasma membrane. Implicated in oculocutaneous albinism. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000157 (23/1461656) while in subpopulation EAS AF= 0.000529 (21/39674). AF 95% confidence interval is 0.000355. There are 0 homozygotes in gnomad4_exome. There are 12 alleles in male gnomad4_exome subpopulation. Median coverage is 32. 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 |
---|---|---|---|---|---|---|---|
DCT | NM_001922.5 | c.1221G>A | p.Met407Ile | missense_variant | 7/8 | ENST00000377028.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DCT | ENST00000377028.10 | c.1221G>A | p.Met407Ile | missense_variant | 7/8 | 1 | NM_001922.5 | P1 | |
DCT | ENST00000446125.1 | c.1320G>A | p.Met440Ile | missense_variant | 9/10 | 1 | |||
DCT | ENST00000483392.6 | c.*96G>A | 3_prime_UTR_variant, NMD_transcript_variant | 8/9 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250850Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135534
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GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461656Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727114
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GnomAD4 genome Cov.: 32
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32
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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 | Jul 19, 2023 | The c.1320G>A (p.M440I) alteration is located in exon 9 (coding exon 9) of the DCT gene. This alteration results from a G to A substitution at nucleotide position 1320, causing the methionine (M) at amino acid position 440 to be replaced by an isoleucine (I). 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
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Gain of methylation at K408 (P = 0.0253);.;
MVP
MPC
0.040
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -23
Find out detailed SpliceAI scores and Pangolin per-transcript scores at