rs1279138

Variant names:

• chr10-12069091-T-A
• rs1279138
• NM_018706.7:c.58T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-12069091-T-A
• chr10-12069091-T-C
• chr10-12069091-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018706.7(DHTKD1):​c.58T>A​(p.Phe20Ile) 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 benign outcome for this variant. 14/21 in silico tools predict 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. F20L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DHTKD1 NM_018706.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045202225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHTKD1	NM_018706.7	c.58T>A	p.Phe20Ile	missense_variant	Exon 1 of 17	ENST00000263035.9	NP_061176.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHTKD1	ENST00000263035.9	c.58T>A	p.Phe20Ile	missense_variant	Exon 1 of 17	1	NM_018706.7	ENSP00000263035.4
DHTKD1	ENST00000437298.1	c.58T>A	p.Phe20Ile	missense_variant	Exon 1 of 5	3		ENSP00000388163.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD3 exomes AF: 0.00000409 AC: 1 AN: 244766 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133716

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000911

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1460294 Hom.: 0 Cov.: 61 AF XY: 0.00 AC XY: 0 AN XY: 726448

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.7
DANN	Benign	0.87
DEOGEN2	Benign	0.00016	T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.23	N;N
REVEL	Benign	0.049
Sift	Benign	0.41	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.0	B;.
Vest4		0.14
MutPred		0.54		Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);
MVP		0.014
MPC		0.16
ClinPred		0.035	T
GERP RS		-0.088
Varity_R		0.052
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs1279138; hg19: chr10-12111090;