18-63655746-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006919.3(SERPINB3):c.1084G>A(p.Glu362Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00694 in 1,613,880 control chromosomes in the GnomAD database, including 54 homozygotes. 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (52 hom.)
• Consequence: SERPINB3 NM_006919.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007921547).
• BP6: Variant 18-63655746-C-T is Benign according to our data. Variant chr18-63655746-C-T is described in ClinVar as [Benign]. Clinvar id is 774727.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB3	NM_006919.3	c.1084G>A	p.Glu362Lys	missense_variant	8/8	ENST00000283752.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB3	ENST00000283752.10	c.1084G>A	p.Glu362Lys	missense_variant	8/8	1	NM_006919.3	P1
SERPINB3	ENST00000332821.8	c.928G>A	p.Glu310Lys	missense_variant	7/7	1
SERPINB11	ENST00000489748.5	c.-246C>T		5_prime_UTR_variant	2/7	2

Frequencies

GnomAD3 genomes AF: 0.00459 AC: 698 AN: 152010 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00400

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00782

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00586 AC: 1471 AN: 251080 Hom.: 8 AF XY: 0.00611 AC XY: 829 AN XY: 135686

Gnomad AFR exome AF: 0.00124

Gnomad AMR exome AF: 0.00310

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00611

Gnomad FIN exome AF: 0.00383

Gnomad NFE exome AF: 0.00910

Gnomad OTH exome AF: 0.00636

GnomAD4 exome AF: 0.00718 AC: 10500 AN: 1461752 Hom.: 52 Cov.: 31 AF XY: 0.00713 AC XY: 5184 AN XY: 727178

Gnomad4 AFR exome AF: 0.00120

Gnomad4 AMR exome AF: 0.00302

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00623

Gnomad4 FIN exome AF: 0.00432

Gnomad4 NFE exome AF: 0.00825

Gnomad4 OTH exome AF: 0.00598

GnomAD4 genome AF: 0.00459 AC: 698 AN: 152128 Hom.: 2 Cov.: 32 AF XY: 0.00440 AC XY: 327 AN XY: 74374

Gnomad4 AFR AF: 0.00109

Gnomad4 AMR AF: 0.00399

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00664

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.00782

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00646 Hom.: 11

Bravo AF: 0.00462

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00882 AC: 34

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00814 AC: 70

ExAC AF: 0.00657 AC: 798

Asia WGS AF: 0.00202 AC: 7 AN: 3476

EpiCase AF: 0.00693

EpiControl AF: 0.00694

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	0.11
Dann	Benign	0.94
DEOGEN2	Benign	0.10	T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.19	T;T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.0079	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.98	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.28
Sift	Benign	0.56	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.73	P;B
Vest4		0.11
MVP		0.65
MPC		0.029
ClinPred		0.0076	T
GERP RS		-3.3
Varity_R		0.17
gMVP		0.27

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

LitVar

Other links and lift over

dbSNP: rs12953909; hg19: chr18-61322980;