chr18-63595113-G-A

Position:

• chr18-63595113-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012397.4(SERPINB13):​c.700G>A​(p.Gly234Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINB13 NM_012397.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB13	NM_012397.4	c.700G>A	p.Gly234Arg	missense_variant	7/8	ENST00000344731.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB13	ENST00000344731.10	c.700G>A	p.Gly234Arg	missense_variant	7/8	1	NM_012397.4	P1
SERPINB13	ENST00000269489.9	c.727G>A	p.Gly243Arg	missense_variant	7/8	1
SERPINB13	ENST00000438844.1	c.*412G>A		3_prime_UTR_variant, NMD_transcript_variant	8/9	1
SERPINB13	ENST00000415733.1	c.247G>A	p.Gly83Arg	missense_variant	3/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2023

The c.700G>A (p.G234R) alteration is located in exon 7 (coding exon 6) of the SERPINB13 gene. This alteration results from a G to A substitution at nucleotide position 700, causing the glycine (G) at amino acid position 234 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Uncertain	0.13	D
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.34	T
Sift4G	Uncertain	0.059	T;T;T
Polyphen		0.41	.;B;.
Vest4		0.23
MutPred		0.59		.;Loss of methylation at K231 (P = 0.0893);.;
MVP		0.82
MPC		0.087
ClinPred		0.89	D
GERP RS		5.8
Varity_R		0.57
gMVP		0.42

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-61262347;