Variant 18-63793242-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003784.4(SERPINB7):c.301G>A(p.Gly101Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000436 in 1,605,522 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SERPINB7
NM_003784.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37

Variant links:

Genes affected

SERPINB7 (HGNC:13902): (serpin family B member 7) This gene encodes a member of a family of proteins which function as protease inhibitors. Expression of this gene is upregulated in IgA nephropathy and mutations have been found to cause palmoplantar keratoderma, Nagashima type. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

SERPINB7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB7	NM_003784.4 linkuse as main transcript	c.301G>A	p.Gly101Arg	missense_variant	4/8	ENST00000398019.7	NP_003775.1	O75635-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB7	ENST00000398019.7 linkuse as main transcript	c.301G>A	p.Gly101Arg	missense_variant	4/8	1	NM_003784.4	ENSP00000381101.2		O75635-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

247394

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000220

Gnomad SAS 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:

0.00000413

AC:

AN:

1453386

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2024

The c.301G>A (p.G101R) alteration is located in exon 4 (coding exon 3) of the SERPINB7 gene. This alteration results from a G to A substitution at nucleotide position 301, causing the glycine (G) at amino acid position 101 to be replaced by an arginine (R). 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

Pathogenic

0.57

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.036

.;T;.;T;.;T;T

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.85

T;T;T;.;T;.;T

M_CAP

Benign

0.068

MetaRNN

Uncertain

0.64

D;D;D;D;D;D;D

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.38

.;N;.;N;.;N;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

3.4

N;N;N;N;N;N;N

REVEL

Uncertain

0.47

Sift

Benign

1.0

T;T;T;T;T;T;T

Sift4G

Benign

0.27

T;T;T;T;D;T;T

Polyphen

1.0

.;D;.;D;.;D;.

Vest4

0.48, 0.44, 0.47

MutPred

0.81

Loss of catalytic residue at L102 (P = 0.1187);Loss of catalytic residue at L102 (P = 0.1187);.;Loss of catalytic residue at L102 (P = 0.1187);Loss of catalytic residue at L102 (P = 0.1187);Loss of catalytic residue at L102 (P = 0.1187);Loss of catalytic residue at L102 (P = 0.1187);

MVP

0.82

MPC

0.18

ClinPred

0.31

GERP RS

5.9

Varity_R

0.16

gMVP

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over