19-51016090-G-T

Variant names:

• chr19-51016090-G-T
• rs1061368
• NM_145888.3:c.336C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_145888.3(KLK10):​c.336C>A​(p.Thr112Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,424,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KLK10 NM_145888.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451
• Publications: 21 publications found

Genes affected

KLK10 (HGNC:6358): (kallikrein related peptidase 10) 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. Its encoded protein is secreted and may play a role in suppression of tumorigenesis in breast and prostate cancers. Alternate splicing of this gene results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.451 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK10	NM_145888.3	c.336C>A	p.Thr112Thr	synonymous_variant	Exon 4 of 6	ENST00000358789.8	NP_665895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK10	ENST00000358789.8	c.336C>A	p.Thr112Thr	synonymous_variant	Exon 4 of 6	1	NM_145888.3	ENSP00000351640.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00 AC: 0 AN: 191352 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1424334 Hom.: 0 Cov.: 53 AF XY: 0.00000284 AC XY: 2 AN XY: 705228

African (AFR) AF: 0.0000309 AC: 1 AN: 32370

American (AMR) AF: 0.00 AC: 0 AN: 38804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25492

East Asian (EAS) AF: 0.00 AC: 0 AN: 37532

South Asian (SAS) AF: 0.00 AC: 0 AN: 81410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1093144

Other (OTH) AF: 0.0000169 AC: 1 AN: 59030

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.34
PhyloP100		-0.45

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

Other links and lift over

dbSNP: rs1061368; hg19: chr19-51519346;