7-128877134-G-A

Position:

• chr7-128877134-G-A

Variant summary

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

The NM_001366122.1(KCP):​c.4796C>T​(p.Pro1599Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,355,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: KCP NM_001366122.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

Genes affected

KCP (HGNC:17585): (kielin cysteine rich BMP regulator) Predicted to act upstream of or within hematopoietic progenitor cell differentiation and positive regulation of BMP signaling pathway. Predicted to be located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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=0.17308971).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCP	NM_001366122.1	c.4796C>T	p.Pro1599Leu	missense_variant	40/40	ENST00000610776.5	NP_001353051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCP	ENST00000610776.5	c.4796C>T	p.Pro1599Leu	missense_variant	40/40	5	NM_001366122.1	ENSP00000479679.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000959 AC: 13 AN: 1355824 Hom.: 0 Cov.: 32 AF XY: 0.0000105 AC XY: 7 AN XY: 666036

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000113

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000161

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000151

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2024

The c.4421C>T (p.P1474L) alteration is located in exon 36 (coding exon 36) of the KCP gene. This alteration results from a C to T substitution at nucleotide position 4421, causing the proline (P) at amino acid position 1474 to be replaced by a leucine (L). 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	0.071
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	18
DANN	Benign	0.81
DEOGEN2	Benign	0.032	T;.;T
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.82	T;T;T
MetaRNN	Benign	0.17	T;T;T
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.085	T;T;T
Vest4		0.15
MVP		0.42
GERP RS		4.4
Varity_R		0.20
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs1008384302; hg19: chr7-128517188;