18-63710345-A-T

Position:

• chr18-63710345-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370475.1(SERPINB11):​c.152A>T​(p.Glu51Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SERPINB11 NM_001370475.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.694

Genes affected

SERPINB11 (HGNC:14221): (serpin family B member 11) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in cytoplasm. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SERPINB11 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20685422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB11	NM_001370475.1	c.152A>T	p.Glu51Val	missense_variant	2/8	ENST00000544088.6	NP_001357404.1
SERPINB11	NM_080475.5	c.152A>T	p.Glu51Val	missense_variant	3/9		NP_536723.2
SERPINB11	NM_001291278.2	c.152A>T	p.Glu51Val	missense_variant	2/6		NP_001278207.1
SERPINB11	NM_001291279.2	c.-256A>T		5_prime_UTR_variant	2/7		NP_001278208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB11	ENST00000544088.6	c.152A>T	p.Glu51Val	missense_variant	2/8	2	NM_001370475.1	ENSP00000441497.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460064 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 726316

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	18
DANN	Benign	0.94
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.31	T;.;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Uncertain	0.15	D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.53	.;.;N;.;.
REVEL	Uncertain	0.31
Sift4G	Benign	0.15	T;D;D;D;T
Vest4		0.16, 0.22, 0.25
MutPred		0.50		Loss of solvent accessibility (P = 0.0052);Loss of solvent accessibility (P = 0.0052);Loss of solvent accessibility (P = 0.0052);Loss of solvent accessibility (P = 0.0052);Loss of solvent accessibility (P = 0.0052);
MVP		0.45
MPC		0.013
ClinPred		0.95	D
GERP RS		4.3
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1395268; hg19: chr18-61377579;