18-63594479-G-A

Variant names:

• chr18-63594479-G-A
• rs377348890
• NM_012397.4:c.597G>A

Variant summary

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

The NM_012397.4(SERPINB13):​c.597G>A​(p.Glu199Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,662 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: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SERPINB13 NM_012397.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857
• Publications: 9 publications found

Genes affected

SERPINB13 (HGNC:8944): (serpin family B member 13) The protein encoded by this gene is a member of the serpin family of serine protease inhibitors. The encoded protein inhibits the activity of cathepsin K and is itself transcriptionally repressed by RUNX1. This gene is downregulated in many types of cancer. [provided by RefSeq, Jan 2017]

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=-0.74).
• BP7: Synonymous conserved (PhyloP=-0.857 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012397.4. 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
	SERPINB13	NM_012397.4	MANE Select	c.597G>A	p.Glu199Glu	synonymous	Exon 6 of 8	NP_036529.1	Q9UIV8-1
	SERPINB13	NM_001307923.2		c.624G>A	p.Glu208Glu	synonymous	Exon 6 of 8	NP_001294852.1	A0A0A0MQW3
	SERPINB13	NM_001348267.2		c.189G>A	p.Glu63Glu	synonymous	Exon 5 of 7	NP_001335196.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB13	ENST00000344731.10	TSL:1 MANE Select	c.597G>A	p.Glu199Glu	synonymous	Exon 6 of 8	ENSP00000341584.6	Q9UIV8-1
	SERPINB13	ENST00000269489.9	TSL:1	c.624G>A	p.Glu208Glu	synonymous	Exon 6 of 8	ENSP00000269489.6	A0A0A0MQW3
	SERPINB13	ENST00000438844.1	TSL:1	n.*309G>A		non_coding_transcript_exon	Exon 7 of 9	ENSP00000394592.1	F8WE70

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461662 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

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

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111924

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.5
DANN	Benign	0.57
PhyloP100		-0.86

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: rs377348890; hg19: chr18-61261713; COSMIC: COSV54030788; COSMIC: COSV54030788;