rs2271092

Variant names:

• chr19-50856287-G-A
• rs2271092
• NM_001648.2:c.94G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-50856287-G-A
• chr19-50856287-G-C
• chr19-50856287-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001648.2(KLK3):​c.94G>A​(p.Glu32Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,613,256 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (16 hom., cov: 31)
  • Exomes 𝑓: 0.0020 (78 hom.)
• Consequence: KLK3 NM_001648.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.38
• Publications: 7 publications found

Genes affected

KLK3 (HGNC:6364): (kallikrein related peptidase 3) 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. The gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. It encodes a single-chain glycoprotein, a protease which is synthesized in the epithelial cells of the prostate gland, and is present in seminal plasma. It is thought to function normally in the liquefaction of seminal coagulum, presumably by hydrolysis of the high molecular mass seminal vesicle protein. The serum level of this protein, called PSA in the clinical setting, is useful in the diagnosis and monitoring of prostatic carcinoma. Alternate splicing of this gene generates several transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004591286).
• BP6: Variant 19-50856287-G-A is Benign according to our data. Variant chr19-50856287-G-A is described in ClinVar as Benign. ClinVar VariationId is 784838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001648.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	NM_001648.2	MANE Select	c.94G>A	p.Glu32Lys	missense	Exon 2 of 5	NP_001639.1	Q546G3
	KLK3	NM_001030047.1		c.94G>A	p.Glu32Lys	missense	Exon 2 of 5	NP_001025218.1	P07288-2
	KLK3	NM_001030048.1		c.94G>A	p.Glu32Lys	missense	Exon 2 of 5	NP_001025219.1	P07288-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	ENST00000326003.7	TSL:1 MANE Select	c.94G>A	p.Glu32Lys	missense	Exon 2 of 5	ENSP00000314151.1	P07288-1
	KLK3	ENST00000360617.7	TSL:1	c.94G>A	p.Glu32Lys	missense	Exon 2 of 5	ENSP00000353829.2	P07288-2
	KLK3	ENST00000593997.5	TSL:1	c.94G>A	p.Glu32Lys	missense	Exon 2 of 4	ENSP00000472907.1	P07288-5

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 536 AN: 152190 Hom.: 15 Cov.: 31

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0302

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00695

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00816 AC: 2050 AN: 251328 AF XY: 0.00628

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.0550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00533

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00522

GnomAD4 exome AF: 0.00197 AC: 2877 AN: 1460948 Hom.: 78 Cov.: 32 AF XY: 0.00172 AC XY: 1248 AN XY: 726806

African (AFR) AF: 0.000389 AC: 13 AN: 33446

American (AMR) AF: 0.0543 AC: 2429 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00645 AC: 256 AN: 39698

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5068

European-Non Finnish (NFE) AF: 0.0000468 AC: 52 AN: 1111952

Other (OTH) AF: 0.00197 AC: 119 AN: 60320

GnomAD4 genome AF: 0.00357 AC: 543 AN: 152308 Hom.: 16 Cov.: 31 AF XY: 0.00385 AC XY: 287 AN XY: 74464

African (AFR) AF: 0.000601 AC: 25 AN: 41572

American (AMR) AF: 0.0306 AC: 469 AN: 15302

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

East Asian (EAS) AF: 0.00697 AC: 36 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.000940 Hom.: 3

Bravo AF: 0.00617

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00599 AC: 727

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	0.24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.049	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	-0.15	N
PhyloP100		-3.4
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.40
Sift	Benign	0.23	T
Sift4G	Benign	0.65	T
Polyphen		0.92	P
Vest4		0.16
MVP		0.77
MPC		0.40
ClinPred		0.054	T
GERP RS		-4.2
Varity_R		0.21
gMVP		0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs2271092; hg19: chr19-51359543;