19-43527144-G-T

Variant names:

• chr19-43527144-G-T
• NM_014297.5:c.34C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014297.5(ETHE1):​c.34C>A​(p.Gln12Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ETHE1 NM_014297.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29

Genes affected

ETHE1 (HGNC:23287): (ETHE1 persulfide dioxygenase) This gene encodes a member of the metallo beta-lactamase family of iron-containing proteins involved in the mitochondrial sulfide oxidation pathway. The encoded protein catalyzes the oxidation of a persulfide substrate to sulfite. Certain mutations in this gene cause ethylmalonic encephalopathy, an infantile metabolic disorder affecting the brain, gastrointestinal tract and peripheral vessels. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

ZNF575 (HGNC:27606): (zinc finger protein 575) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22978437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETHE1	NM_014297.5	c.34C>A	p.Gln12Lys	missense_variant	Exon 1 of 7	ENST00000292147.7	NP_055112.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETHE1	ENST00000292147.7	c.34C>A	p.Gln12Lys	missense_variant	Exon 1 of 7	1	NM_014297.5	ENSP00000292147.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396248 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 689910

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: 0.0000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.25	T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.66	T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.21	N;.
REVEL	Uncertain	0.31
Sift	Benign	0.29	T;.
Sift4G	Benign	0.32	T;T
Polyphen		0.0020	B;.
Vest4		0.32
MutPred		0.49		Loss of helix (P = 3e-04);Loss of helix (P = 3e-04);
MVP		0.85
MPC		0.71
ClinPred		0.13	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.15
gMVP		0.84

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: chr19-44031296; COSMIC: COSV52678502;