13-94462026-A-C

Position:

• chr13-94462026-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001922.5(DCT):​c.1027T>G​(p.Ser343Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 6.92

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCT	NM_001922.5	c.1027T>G	p.Ser343Ala	missense_variant	5/8	ENST00000377028.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCT	ENST00000377028.10	c.1027T>G	p.Ser343Ala	missense_variant	5/8	1	NM_001922.5	P1
DCT	ENST00000446125.1	c.1027T>G	p.Ser343Ala	missense_variant	5/10	1
DCT	ENST00000483392.6	c.457T>G	p.Ser153Ala	missense_variant, NMD_transcript_variant	4/9	5

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

Mar 01, 2023

The c.1027T>G (p.S343A) alteration is located in exon 5 (coding exon 5) of the DCT gene. This alteration results from a T to G substitution at nucleotide position 1027, causing the serine (S) at amino acid position 343 to be replaced by an alanine (A). 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	Benign	0.15
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Uncertain	0.72	D;.
Eigen	Benign	-0.093
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.67	T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Uncertain	0.71	D
MutationAssessor	Benign	1.3	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.79	N;N
REVEL	Uncertain	0.56
Sift	Benign	0.77	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.0040	B;.
Vest4		0.53
MutPred		0.65		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.80
MPC		0.067
ClinPred		0.79	D
GERP RS		5.5
Varity_R		0.21
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr13-95114280;