chr19-10489655-G-T

Variant names:

• chr19-10489655-G-T
• NM_203500.2:c.1524C>A

Variant summary

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

The NM_203500.2(KEAP1):​c.1524C>A​(p.Ser508Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KEAP1 NM_203500.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEAP1	NM_203500.2	c.1524C>A	p.Ser508Arg	missense_variant	Exon 4 of 6	ENST00000171111.10	NP_987096.1
KEAP1	NM_012289.4	c.1524C>A	p.Ser508Arg	missense_variant	Exon 4 of 6		NP_036421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KEAP1	ENST00000171111.10	c.1524C>A	p.Ser508Arg	missense_variant	Exon 4 of 6	1	NM_203500.2	ENSP00000171111.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;D
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.78	.;T
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		1.0	D;D
Vest4		0.53
MutPred		0.73		Gain of MoRF binding (P = 0.0176);Gain of MoRF binding (P = 0.0176);
MVP		0.86
MPC		2.3
ClinPred		0.93	D
GERP RS		-3.2
Varity_R		0.95
gMVP		0.94

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: chr19-10600331;