chr18-63655680-A-C

Variant names:

• chr18-63655680-A-C
• rs1913472334
• NM_006919.3:c.1150T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006919.3(SERPINB3):​c.1150T>G​(p.Tyr384Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,932 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y384H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SERPINB3 NM_006919.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006919.3. 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
	SERPINB3	NM_006919.3	MANE Select	c.1150T>G	p.Tyr384Asp	missense	Exon 8 of 8	NP_008850.1	P29508-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB3	ENST00000283752.10	TSL:1 MANE Select	c.1150T>G	p.Tyr384Asp	missense	Exon 8 of 8	ENSP00000283752.5	P29508-1
	SERPINB3	ENST00000332821.8	TSL:1	c.994T>G	p.Tyr332Asp	missense	Exon 7 of 7	ENSP00000329498.8	P29508-2
	SERPINB3	ENST00000864639.1		c.1150T>G	p.Tyr384Asp	missense	Exon 8 of 8	ENSP00000534698.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459932 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726078

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 85958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110840

Other (OTH) AF: 0.00 AC: 0 AN: 60318

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	0.0065	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.15
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.38
Sift	Benign	0.066	T
Sift4G	Uncertain	0.040	D
Polyphen		0.99	D
Vest4		0.32
MutPred		0.82		Gain of disorder (P = 0.0123)
MVP		0.64
MPC		0.22
ClinPred		0.71	D
GERP RS		-3.4
Varity_R		0.66
gMVP		0.62

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: rs1913472334; hg19: chr18-61322914;