rs3740015

Variant names:

• chr10-12089082-T-C
• rs3740015
• NM_018706.7:c.814T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-12089082-T-C
• chr10-12089082-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018706.7(DHTKD1):​c.814T>C​(p.Tyr272His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y272D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHTKD1 NM_018706.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.83
• Publications: 37 publications found

Genes affected

DHTKD1 (HGNC:23537): (dehydrogenase E1 and transketolase domain containing 1) This gene encodes a component of a mitochondrial 2-oxoglutarate-dehydrogenase-complex-like protein involved in the degradation pathways of several amino acids, including lysine. Mutations in this gene are associated with 2-aminoadipic 2-oxoadipic aciduria and Charcot-Marie-Tooth Disease Type 2Q. [provided by RefSeq, May 2013]

DHTKD1 Gene-Disease associations (from GenCC):

• 2-aminoadipic 2-oxoadipic aciduria

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Charcot-Marie-Tooth disease axonal type 2Q

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1627667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHTKD1	NM_018706.7	c.814T>C	p.Tyr272His	missense_variant	Exon 5 of 17	ENST00000263035.9	NP_061176.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHTKD1	ENST00000263035.9	c.814T>C	p.Tyr272His	missense_variant	Exon 5 of 17	1	NM_018706.7	ENSP00000263035.4
DHTKD1	ENST00000437298.1	c.619T>C	p.Tyr207His	missense_variant	Exon 4 of 5	3		ENSP00000388163.1
DHTKD1	ENST00000465617.1	n.299+1353T>C		intron_variant	Intron 2 of 3	3
DHTKD1	ENST00000415935.1	c.-93T>C		upstream_gene_variant		2		ENSP00000400625.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.059	T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Uncertain	0.11	D
MutationAssessor	Benign	-0.29	N;.
PhyloP100		6.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	1.1	N;N
REVEL	Benign	0.18
Sift	Benign	0.12	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.0030	B;.
Vest4		0.13
MutPred		0.43		Gain of disorder (P = 0.0127);.;
MVP		0.63
MPC		0.16
ClinPred		0.48	T
GERP RS		4.2
PromoterAI		-0.0070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.51
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs3740015; hg19: chr10-12131081;