rs374670117

Variant names:

• chr7-142943793-G-A
• NM_000420.3:c.1582C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-142943793-G-A
• chr7-142943793-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000420.3(KEL):​c.1582C>T​(p.Pro528Ser) 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 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KEL NM_000420.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06761125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEL	NM_000420.3	c.1582C>T	p.Pro528Ser	missense_variant	Exon 14 of 19	ENST00000355265.7	NP_000411.1
KEL	XM_005249993.2	c.1618C>T	p.Pro540Ser	missense_variant	Exon 14 of 19		XP_005250050.1
KEL	XM_047420357.1	c.1471C>T	p.Pro491Ser	missense_variant	Exon 13 of 18		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KEL	ENST00000355265.7	c.1582C>T	p.Pro528Ser	missense_variant	Exon 14 of 19	1	NM_000420.3	ENSP00000347409.2
KEL	ENST00000465697.1	n.443C>T		non_coding_transcript_exon_variant	Exon 3 of 4	3
KEL	ENST00000470850.1	n.47C>T		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461658 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727134

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.68
DANN	Benign	0.37
DEOGEN2	Benign	0.076	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.073
Sift	Benign	0.50	T
Sift4G	Benign	0.71	T
Polyphen		0.0050	B
Vest4		0.066
MutPred		0.31		Gain of MoRF binding (P = 0.0377);
MVP		0.44
MPC		0.062
ClinPred		0.024	T
GERP RS		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.23

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: chr7-142640880;