chr7-128877661-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366122.1(KCP):ā€‹c.4441A>Gā€‹(p.Ser1481Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,551,392 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.000031 ( 1 hom. )

Consequence

KCP
NM_001366122.1 missense

Scores

1
1
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.210
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.14944246).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KCPNM_001366122.1 linkuse as main transcriptc.4441A>G p.Ser1481Gly missense_variant 39/40 ENST00000610776.5 NP_001353051.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KCPENST00000610776.5 linkuse as main transcriptc.4441A>G p.Ser1481Gly missense_variant 39/405 NM_001366122.1 ENSP00000479679

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000130
AC:
2
AN:
154120
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
81748
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000168
Gnomad OTH exome
AF:
0.000230
GnomAD4 exome
AF:
0.0000314
AC:
44
AN:
1399200
Hom.:
1
Cov.:
32
AF XY:
0.0000304
AC XY:
21
AN XY:
690098
show subpopulations
Gnomad4 AFR exome
AF:
0.0000633
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000102
Gnomad4 OTH exome
AF:
0.0000690
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152192
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000227

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 28, 2023The c.4066A>G (p.S1356G) alteration is located in exon 35 (coding exon 35) of the KCP gene. This alteration results from a A to G substitution at nucleotide position 4066, causing the serine (S) at amino acid position 1356 to be replaced by a glycine (G). 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
0.084
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.11
CADD
Benign
15
DANN
Benign
0.62
DEOGEN2
Benign
0.026
T;.;T
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.61
T;T;T
MetaRNN
Benign
0.15
T;T;T
PrimateAI
Benign
0.39
T
Sift4G
Benign
0.16
T;T;T
Vest4
0.18
MVP
0.37
GERP RS
-3.2
Varity_R
0.17
gMVP
0.26

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs866511239; hg19: chr7-128517715; API