chr19-10489313-G-T

Variant names:

• chr19-10489313-G-T
• NM_203500.2:c.1587C>A

Variant summary

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

The NM_203500.2(KEAP1):​c.1587C>A​(p.Asp529Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KEAP1 NM_203500.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54

Genes affected

KEAP1 (HGNC:23177): (kelch like ECH associated protein 1) This gene encodes a protein containing KELCH-1 like domains, as well as a BTB/POZ domain. Kelch-like ECH-associated protein 1 interacts with NF-E2-related factor 2 in a redox-sensitive manner and the dissociation of the proteins in the cytoplasm is followed by transportation of NF-E2-related factor 2 to the nucleus. This interaction results in the expression of the catalytic subunit of gamma-glutamylcysteine synthetase. Two alternatively spliced transcript variants encoding the same isoform have been found for this gene. [provided by RefSeq, Jul 2008]

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=0.108293295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEAP1	NM_203500.2	c.1587C>A	p.Asp529Glu	missense_variant	Exon 5 of 6	ENST00000171111.10	NP_987096.1
KEAP1	NM_012289.4	c.1587C>A	p.Asp529Glu	missense_variant	Exon 5 of 6		NP_036421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KEAP1	ENST00000171111.10	c.1587C>A	p.Asp529Glu	missense_variant	Exon 5 of 6	1	NM_203500.2	ENSP00000171111.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461862 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.53
DEOGEN2	Benign	0.20	T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.40
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.30	N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.11	N;N
REVEL	Benign	0.15
Sift	Benign	0.95	T;T
Sift4G	Benign	0.91	T;T
Polyphen		0.0010	B;B
Vest4		0.14
MutPred		0.35		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.66
MPC		0.94
ClinPred		0.11	T
GERP RS		3.5
Varity_R		0.36
gMVP		0.15

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: chr19-10599989;