1-241568656-T-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_003679.5(KMO):c.957+9T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,610,304 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (8 hom.)
• Consequence: KMO NM_003679.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.526

Genes affected

KMO (HGNC:6381): (kynurenine 3-monooxygenase) This gene encodes a mitochondrion outer membrane protein that catalyzes the hydroxylation of L-tryptophan metabolite, L-kynurenine, to form L-3-hydroxykynurenine. Studies in yeast identified this gene as a therapeutic target for Huntington disease. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 1-241568656-T-A is Benign according to our data. Variant chr1-241568656-T-A is described in ClinVar as [Benign]. Clinvar id is 773477.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMO	NM_003679.5	c.957+9T>A		intron_variant		ENST00000366559.9
KMO	NM_001410944.1	c.957+9T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMO	ENST00000366559.9	c.957+9T>A		intron_variant		1	NM_003679.5	P2

Frequencies

GnomAD3 genomes AF: 0.00236 AC: 359 AN: 151858 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000607

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00319

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00249 AC: 616 AN: 247382 Hom.: 0 AF XY: 0.00265 AC XY: 355 AN XY: 133798

Gnomad AFR exome AF: 0.000248

Gnomad AMR exome AF: 0.00230

Gnomad ASJ exome AF: 0.00874

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00129

Gnomad FIN exome AF: 0.000652

Gnomad NFE exome AF: 0.00335

Gnomad OTH exome AF: 0.00333

GnomAD4 exome AF: 0.00265 AC: 3866 AN: 1458328 Hom.: 8 Cov.: 31 AF XY: 0.00275 AC XY: 1993 AN XY: 725328

Gnomad4 AFR exome AF: 0.000241

Gnomad4 AMR exome AF: 0.00214

Gnomad4 ASJ exome AF: 0.00975

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00152

Gnomad4 FIN exome AF: 0.000732

Gnomad4 NFE exome AF: 0.00282

Gnomad4 OTH exome AF: 0.00304

GnomAD4 genome AF: 0.00236 AC: 359 AN: 151976 Hom.: 1 Cov.: 32 AF XY: 0.00225 AC XY: 167 AN XY: 74316

Gnomad4 AFR AF: 0.000606

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.0136

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.000660

Gnomad4 NFE AF: 0.00319

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00351 Hom.: 0

Bravo AF: 0.00253

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	15
Dann	Benign	0.79

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: rs187112513; hg19: chr1-241731956;