rs577262694

Variant names:

• chr18-63655875-C-A
• rs577262694
• NM_006919.3:c.955G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-63655875-C-A
• chr18-63655875-C-G
• chr18-63655875-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006919.3(SERPINB3):​c.955G>T​(p.Gly319Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. G319R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SERPINB3 NM_006919.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.64
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16238028).

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.955G>T	p.Gly319Trp	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.955G>T	p.Gly319Trp	missense	Exon 8 of 8	ENSP00000283752.5	P29508-1
	SERPINB3	ENST00000332821.8	TSL:1	c.799G>T	p.Gly267Trp	missense	Exon 7 of 7	ENSP00000329498.8	P29508-2
	SERPINB3	ENST00000864639.1		c.955G>T	p.Gly319Trp	missense	Exon 8 of 8	ENSP00000534698.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 251038 AF XY: 0.00

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461732 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727162

African (AFR) AF: 0.0000598 AC: 2 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111930

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152238 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74438

African (AFR) AF: 0.0000241 AC: 1 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	10
DANN	Benign	0.74
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.064	T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		-4.6
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.32
Sift	Benign	0.043	D
Sift4G	Uncertain	0.019	D
Polyphen		0.0050	B
Vest4		0.27
MutPred		0.52		Loss of disorder (P = 0.0157)
MVP		0.54
MPC		0.026
ClinPred		0.20	T
GERP RS		-5.1
Varity_R		0.37
gMVP		0.54
Mutation Taster		=91/9	polymorphism

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: rs577262694; hg19: chr18-61323109;