7-128877099-C-A

Variant names:

• chr7-128877099-C-A
• rs1323884628
• NM_001366122.1:c.4831G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366122.1(KCP):​c.4831G>T​(p.Asp1611Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. 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. D1611N) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16140208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCP	NM_001366122.1	c.4831G>T	p.Asp1611Tyr	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.4831G>T	p.Asp1611Tyr	missense_variant	Exon 40 of 40	5	NM_001366122.1	ENSP00000479679.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000814 AC: 1 AN: 122882 AF XY: 0.0000152

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000199

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1366456 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 673208

African (AFR) AF: 0.00 AC: 0 AN: 29448

American (AMR) AF: 0.00 AC: 0 AN: 24732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23394

East Asian (EAS) AF: 0.00 AC: 0 AN: 35432

South Asian (SAS) AF: 0.00 AC: 0 AN: 74252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5428

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069250

Other (OTH) AF: 0.00 AC: 0 AN: 56544

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	16
DANN	Benign	0.77
DEOGEN2	Benign	0.025	T;.;T
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.78	T;T;T
MetaRNN	Benign	0.16	T;T;T
PhyloP100		0.086
PrimateAI	Benign	0.38	T
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.35
MVP		0.36
GERP RS		3.5
Varity_R		0.052
gMVP		0.51
Mutation Taster		=100/0	polymorphism

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: rs1323884628; hg19: chr7-128517153;