7-128877636-G-T

Variant names:

• chr7-128877636-G-T
• rs368508165
• NM_001366122.1:c.4466C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001366122.1(KCP):​c.4466C>A​(p.Pro1489Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,314 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1489L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: KCP NM_001366122.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.82
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCP	NM_001366122.1	c.4466C>A	p.Pro1489Gln	missense_variant	Exon 39 of 40	ENST00000610776.5	NP_001353051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCP	ENST00000610776.5	c.4466C>A	p.Pro1489Gln	missense_variant	Exon 39 of 40	5	NM_001366122.1	ENSP00000479679.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399314 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690166

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078970

Other (OTH) AF: 0.00 AC: 0 AN: 58012

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	25
DANN	Benign	0.90
DEOGEN2	Benign	0.26	T;.;T
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.83	T;T;T
MetaRNN	Uncertain	0.70	D;D;D
PhyloP100		7.8
PrimateAI	Uncertain	0.59	T
Sift4G	Pathogenic	0.0010	D;D;D
Vest4		0.66
MVP		0.32
GERP RS		4.8
Varity_R		0.21
gMVP		0.68
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.38		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs368508165; hg19: chr7-128517690;