NM_145888.3:c.318A>G

Variant names:

• chr19-51016108-T-C
• rs2075688
• NM_145888.3:c.318A>G

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.318A>G​(p.Gly106Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,882 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: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: KLK10 NM_145888.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.93
• Publications: 18 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=-0.88).
• BP7: Synonymous conserved (PhyloP=-4.93 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145888.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK10	NM_145888.3	MANE Select	c.318A>G	p.Gly106Gly	synonymous	Exon 4 of 6	NP_665895.1
	KLK10	NM_001077500.2		c.318A>G	p.Gly106Gly	synonymous	Exon 4 of 6	NP_001070968.1
	KLK10	NM_002776.5		c.318A>G	p.Gly106Gly	synonymous	Exon 4 of 6	NP_002767.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK10	ENST00000358789.8	TSL:1 MANE Select	c.318A>G	p.Gly106Gly	synonymous	Exon 4 of 6	ENSP00000351640.2
	KLK10	ENST00000309958.7	TSL:1	c.318A>G	p.Gly106Gly	synonymous	Exon 4 of 6	ENSP00000311746.2
	KLK10	ENST00000601467.1	TSL:1	n.26A>G		non_coding_transcript_exon	Exon 3 of 5	ENSP00000472773.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428882 Hom.: 0 Cov.: 48 AF XY: 0.00000141 AC XY: 1 AN XY: 707786

African (AFR) AF: 0.00 AC: 0 AN: 32506

American (AMR) AF: 0.00 AC: 0 AN: 39702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25548

East Asian (EAS) AF: 0.00 AC: 0 AN: 37776

South Asian (SAS) AF: 0.00 AC: 0 AN: 81910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095624

Other (OTH) AF: 0.00 AC: 0 AN: 59212

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.60
PhyloP100		-4.9

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: rs2075688; hg19: chr19-51519364;