rs1568207063

Variant names:

• chr18-63782493-C-G
• rs1568207063
• NM_003784.4:c.121C>G

Variant summary

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

The NM_003784.4(SERPINB7):​c.121C>G​(p.Leu41Val) 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 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SERPINB7 NM_003784.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.441
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• palmoplantar keratoderma, Nagashima type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet

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_003784.4. 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
	SERPINB7	NM_003784.4	MANE Select	c.121C>G	p.Leu41Val	missense	Exon 2 of 8	NP_003775.1	O75635-1
	SERPINB7	NM_001040147.3		c.121C>G	p.Leu41Val	missense	Exon 2 of 8	NP_001035237.1	O75635-1
	SERPINB7	NM_001261830.2		c.121C>G	p.Leu41Val	missense	Exon 2 of 8	NP_001248759.1	O75635-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB7	ENST00000398019.7	TSL:1 MANE Select	c.121C>G	p.Leu41Val	missense	Exon 2 of 8	ENSP00000381101.2	O75635-1
	SERPINB7	ENST00000336429.6	TSL:1	c.121C>G	p.Leu41Val	missense	Exon 2 of 8	ENSP00000337212.2	O75635-1
	SERPINB7	ENST00000546027.5	TSL:2	c.121C>G	p.Leu41Val	missense	Exon 2 of 8	ENSP00000444861.1	O75635-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251354 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461720 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727174

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111920

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	3.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.44
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.35
Sift	Benign	0.063	T
Sift4G	Uncertain	0.026	D
Polyphen		0.10	B
Vest4		0.22
MutPred		0.75		Gain of methylation at R43 (P = 0.1152)
MVP		0.44
MPC		0.023
ClinPred		0.24	T
GERP RS		-0.49
Varity_R		0.13
gMVP		0.20
Mutation Taster		=82/18	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: rs1568207063; hg19: chr18-61449727;