7-142942444-C-T

Variant names:

• chr7-142942444-C-T
• rs61729051
• NM_000420.3:c.2027G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000420.3(KEL):​c.2027G>A​(p.Ser676Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000347 in 1,442,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000035 (0 hom.)
• Consequence: KEL NM_000420.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEL	NM_000420.3	c.2027G>A	p.Ser676Asn	missense_variant	Exon 18 of 19	ENST00000355265.7	NP_000411.1
KEL	XM_005249993.2	c.2063G>A	p.Ser688Asn	missense_variant	Exon 18 of 19		XP_005250050.1
KEL	XM_047420357.1	c.1916G>A	p.Ser639Asn	missense_variant	Exon 17 of 18		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KEL	ENST00000355265.7	c.2027G>A	p.Ser676Asn	missense_variant	Exon 18 of 19	1	NM_000420.3	ENSP00000347409.2
KEL	ENST00000470850.1	n.327G>A		non_coding_transcript_exon_variant	Exon 4 of 4	2
KEL	ENST00000478969.1	n.*15G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000347 AC: 5 AN: 1442490 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 715510

African (AFR) AF: 0.00 AC: 0 AN: 33282

American (AMR) AF: 0.00 AC: 0 AN: 42424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25668

East Asian (EAS) AF: 0.00 AC: 0 AN: 39178

South Asian (SAS) AF: 0.00 AC: 0 AN: 83324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52076

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5732

European-Non Finnish (NFE) AF: 0.00000363 AC: 4 AN: 1101258

Other (OTH) AF: 0.00 AC: 0 AN: 59548

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000238 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.079	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.32	D
MutationAssessor	Benign	2.0	M
PhyloP100		4.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.53
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.76		Loss of catalytic residue at S676 (P = 0.0488);
MVP		0.97
MPC		0.37
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.60
gMVP		0.53
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs61729051; hg19: chr7-142639531;