7-142943032-C-A

Variant names:

• chr7-142943032-C-A
• NM_000420.3:c.1784G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000420.3(KEL):​c.1784G>T​(p.Gly595Val) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KEL NM_000420.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14

Genes affected

KEL (HGNC:6308): (Kell metallo-endopeptidase (Kell blood group)) This gene encodes a type II transmembrane glycoprotein that is the highly polymorphic Kell blood group antigen. The Kell glycoprotein links via a single disulfide bond to the XK membrane protein that carries the Kx antigen. The encoded protein contains sequence and structural similarity to members of the neprilysin (M13) family of zinc endopeptidases. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.903

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEL	NM_000420.3	c.1784G>T	p.Gly595Val	missense_variant	Exon 17 of 19	ENST00000355265.7	NP_000411.1
KEL	XM_005249993.2	c.1820G>T	p.Gly607Val	missense_variant	Exon 17 of 19		XP_005250050.1
KEL	XM_047420357.1	c.1673G>T	p.Gly558Val	missense_variant	Exon 16 of 18		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KEL	ENST00000355265.7	c.1784G>T	p.Gly595Val	missense_variant	Exon 17 of 19	1	NM_000420.3	ENSP00000347409.2
KEL	ENST00000478969.1	n.123G>T		non_coding_transcript_exon_variant	Exon 1 of 2	3
KEL	ENST00000470850.1	n.169-85G>T		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1784G>T (p.G595V) alteration is located in exon 17 (coding exon 17) of the KEL gene. This alteration results from a G to T substitution at nucleotide position 1784, causing the glycine (G) at amino acid position 595 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	20
DANN	Benign	0.88
DEOGEN2	Pathogenic	0.80	D
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.74		Loss of helix (P = 0.0196);
MVP		0.85
MPC		0.38
ClinPred		0.97	D
GERP RS		0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr7-142640119;