rs1054713

Variant names:

• chr19-50820245-A-C
• rs1054713
• NM_002257.4:c.405T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-50820245-A-C
• chr19-50820245-A-G
• chr19-50820245-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002257.4(KLK1):​c.405T>G​(p.Asp135Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KLK1 NM_002257.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.10
• Publications: 0 publications found

Genes affected

KLK1 (HGNC:6357): (kallikrein 1) Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. This protein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. [provided by RefSeq, Jul 2008]

KLK1 Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056883454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK1	NM_002257.4	c.405T>G	p.Asp135Glu	missense_variant	Exon 3 of 5	ENST00000301420.3	NP_002248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK1	ENST00000301420.3	c.405T>G	p.Asp135Glu	missense_variant	Exon 3 of 5	1	NM_002257.4	ENSP00000301420.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461734 Hom.: 0 Cov.: 54 AF XY: 0.00 AC XY: 0 AN XY: 727146

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111880

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0010
DANN	Benign	0.66
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.17	N
PhyloP100		-5.1
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.018
Sift	Benign	0.20	T
Sift4G	Benign	0.53	T
Polyphen		0.011	B
Vest4		0.056
MutPred		0.41		Gain of disorder (P = 0.1316);
MVP		0.34
MPC		0.21
ClinPred		0.096	T
GERP RS		-5.8
Varity_R		0.21
gMVP		0.28
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1054713; hg19: chr19-51323501;