7-128877129-C-T

Variant names:

• chr7-128877129-C-T
• rs202223303
• NM_001366122.1:c.4801G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001366122.1(KCP):​c.4801G>A​(p.Glu1601Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00054 in 1,510,234 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00057 (1 hom.)
• Consequence: KCP NM_001366122.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.539
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07400051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCP	NM_001366122.1	c.4801G>A	p.Glu1601Lys	missense_variant	Exon 40 of 40	ENST00000610776.5	NP_001353051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCP	ENST00000610776.5	c.4801G>A	p.Glu1601Lys	missense_variant	Exon 40 of 40	5	NM_001366122.1	ENSP00000479679.1

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000133 AC: 16 AN: 120310 AF XY: 0.000187

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000682

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000286

Gnomad OTH exome AF: 0.000293

GnomAD4 exome AF: 0.000568 AC: 771 AN: 1358032 Hom.: 1 Cov.: 32 AF XY: 0.000536 AC XY: 358 AN XY: 667366

African (AFR) AF: 0.000102 AC: 3 AN: 29384

American (AMR) AF: 0.0000823 AC: 2 AN: 24308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23014

East Asian (EAS) AF: 0.0000851 AC: 3 AN: 35262

South Asian (SAS) AF: 0.00 AC: 0 AN: 73656

European-Finnish (FIN) AF: 0.0000209 AC: 1 AN: 47782

Middle Eastern (MID) AF: 0.000372 AC: 2 AN: 5370

European-Non Finnish (NFE) AF: 0.000684 AC: 727 AN: 1063158

Other (OTH) AF: 0.000588 AC: 33 AN: 56098

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.000256 AC XY: 19 AN XY: 74346

African (AFR) AF: 0.000169 AC: 7 AN: 41440

American (AMR) AF: 0.000196 AC: 3 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000562 Hom.: 0

Bravo AF: 0.000291

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000314 AC: 1

ExAC AF: 0.0000823 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4426G>A (p.E1476K) alteration is located in exon 36 (coding exon 36) of the KCP gene. This alteration results from a G to A substitution at nucleotide position 4426, causing the glutamic acid (E) at amino acid position 1476 to be replaced by a lysine (K). 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	0.10
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Benign	0.83
DEOGEN2	Benign	0.027	T;.;T
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.65	T;T;T
MetaRNN	Benign	0.074	T;T;T
PhyloP100		0.54
PrimateAI	Uncertain	0.53	T
Sift4G	Uncertain	0.015	D;D;D
Vest4		0.26
MVP		0.31
GERP RS		4.4
Varity_R		0.050
gMVP		0.45

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: rs202223303; hg19: chr7-128517183;