Genetic Variant NM_001366122.1:c.4747G>T (chr7-128877183-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001366122.1(KCP):c.4747G>T(p.Gly1583Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G1583S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCP
NM_001366122.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.692

Publications

0 publications found

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]

KCP links:

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ACMG classification

Classification was made for transcript

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 link	c.4747G>T	p.Gly1583Cys	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 link	c.4747G>T	p.Gly1583Cys	missense_variant	Exon 40 of 40	5	NM_001366122.1	ENSP00000479679.1		A0A087WVT8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1335128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

653274

African (AFR)

AF:

0.00

AC:

AN:

28790

American (AMR)

AF:

0.00

AC:

AN:

21884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21338

East Asian (EAS)

AF:

0.00

AC:

AN:

35060

South Asian (SAS)

AF:

0.00

AC:

AN:

69466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5100

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1051596

Other (OTH)

AF:

0.00

AC:

AN:

55090

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Pathogenic

0.52

BayesDel_noAF

Pathogenic

0.51

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.34

T;.;T

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

T;T;T

MetaRNN

Uncertain

0.49

T;T;T

PhyloP100

0.69

PrimateAI

Benign

0.46

Sift4G

Uncertain

0.0020

D;D;D

Vest4

0.51

MVP

0.57

GERP RS

2.6

Varity_R

0.15

gMVP

0.68

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over