chr18-63655898-T-A

Position:

• chr18-63655898-T-A

Variant summary

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

The NM_006919.3(SERPINB3):​c.932A>T​(p.Asp311Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SERPINB3 NM_006919.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.588

Genes affected

SERPINB3 (HGNC:10569): (serpin family B member 3) Enables cysteine-type endopeptidase inhibitor activity; protease binding activity; and virus receptor activity. Involved in several processes, including autocrine signaling; paracrine signaling; and regulation of cellular protein metabolic process. Located in cytoplasmic vesicle; extracellular exosome; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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]

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=0.20939127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB3	NM_006919.3	c.932A>T	p.Asp311Val	missense_variant	8/8	ENST00000283752.10	NP_008850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB3	ENST00000283752.10	c.932A>T	p.Asp311Val	missense_variant	8/8	1	NM_006919.3	ENSP00000283752	P1
SERPINB3	ENST00000332821.8	c.776A>T	p.Asp259Val	missense_variant	7/7	1		ENSP00000329498
SERPINB11	ENST00000489748.5	c.-94T>A		5_prime_UTR_variant	2/7	2		ENSP00000480275

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461740 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

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

Mar 25, 2024

The c.932A>T (p.D311V) alteration is located in exon 8 (coding exon 7) of the SERPINB3 gene. This alteration results from a A to T substitution at nucleotide position 932, causing the aspartic acid (D) at amino acid position 311 to be replaced by a valine (V). 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	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	1.2
DANN	Benign	0.86
DEOGEN2	Benign	0.23	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.76	T;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.18
Sift	Benign	0.11	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.0050	B;B
Vest4		0.095
MutPred		0.55		Loss of disorder (P = 0.0429);.;
MVP		0.48
MPC		0.030
ClinPred		0.052	T
GERP RS		-2.5
Varity_R		0.28
gMVP		0.53

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-61323132;