rs567770868

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002640.4(SERPINB8):c.130A>C(p.Met44Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict 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. M44V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SERPINB8
NM_002640.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.465

Publications

0 publications found

Variant links:

Genes affected

SERPINB8 (HGNC:8952): (serpin family B member 8) The protein encoded by this gene is a member of the ov-serpin family of serine protease inhibitors. The encoded protein is produced by platelets and can bind to and inhibit the function of furin, a serine protease involved in platelet functions. In addition, this protein has been found to enhance the mechanical stability of cell-cell adhesion in the skin, and defects in this gene have been associated with an autosomal-recessive form of exfoliative ichthyosis. [provided by RefSeq, Jan 2017]

SERPINB8 links:

HMSD (HGNC:23037): (histocompatibility minor serpin domain containing) This gene encodes a serpin-domain containing protein that may function as a serine protease inhibitor. This gene is primarily expressed in cells of myeloid lineage. A polymorphism in this gene may result in the expression a splice variant that encodes a minor histocompatibility antigen. [provided by RefSeq, Oct 2010]

HMSD links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066102624).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002640.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINB8	NM_002640.4	MANE Select	c.130A>C	p.Met44Leu	missense	Exon 2 of 7	NP_002631.3
SERPINB8	NM_001366198.1		c.130A>C	p.Met44Leu	missense	Exon 2 of 7	NP_001353127.1	P50452-1
SERPINB8	NM_198833.2		c.130A>C	p.Met44Leu	missense	Exon 2 of 7	NP_942130.1	P50452-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINB8	ENST00000397985.7	TSL:1 MANE Select	c.130A>C	p.Met44Leu	missense	Exon 2 of 7	ENSP00000381072.2	P50452-1
SERPINB8	ENST00000397988.7	TSL:1	c.130A>C	p.Met44Leu	missense	Exon 2 of 7	ENSP00000381075.3	P50452-2
SERPINB8	ENST00000353706.6	TSL:5	c.130A>C	p.Met44Leu	missense	Exon 2 of 7	ENSP00000331368.3	P50452-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000387

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

7.5

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.088

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.76

M_CAP

Benign

0.020

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.4

PhyloP100

0.47

PrimateAI

Benign

0.32

PROVEAN

Benign

0.47

REVEL

Benign

0.20

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.15

MutPred

0.69

Loss of catalytic residue at M44 (P = 0.1008)

MVP

0.45

MPC

0.015

ClinPred

0.075

GERP RS

-4.0

Varity_R

0.071

gMVP

0.20

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over