13-94462027-G-T

Position:

• chr13-94462027-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_001922.5(DCT):​c.1026C>A​(p.Asn342Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DCT NM_001922.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.43

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity TYRP2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.839

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCT	NM_001922.5	c.1026C>A	p.Asn342Lys	missense_variant	5/8	ENST00000377028.10	NP_001913.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCT	ENST00000377028.10	c.1026C>A	p.Asn342Lys	missense_variant	5/8	1	NM_001922.5	ENSP00000366227.4
DCT	ENST00000446125.1	c.1026C>A	p.Asn342Lys	missense_variant	5/10	1		ENSP00000392762.1
DCT	ENST00000483392.6	n.456C>A		non_coding_transcript_exon_variant	4/9	5		ENSP00000431275.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.1026C>A (p.N342K) alteration is located in exon 5 (coding exon 5) of the DCT gene. This alteration results from a C to A substitution at nucleotide position 1026, causing the asparagine (N) at amino acid position 342 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	D;.
Eigen	Benign	0.029
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.55
Sift	Benign	0.20	T;T
Sift4G	Benign	0.091	T;T
Polyphen		0.56	P;.
Vest4		0.88
MutPred		0.67		Gain of methylation at N342 (P = 0.0121);Gain of methylation at N342 (P = 0.0121);
MVP		0.83
MPC		0.29
ClinPred		0.96	D
GERP RS		3.5
Varity_R		0.27
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-95114281;