chr18-63979886-T-C

Variant names:

• chr18-63979886-T-C
• NM_002640.4:c.254T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002640.4(SERPINB8):​c.254T>C​(p.Leu85Ser) 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 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SERPINB8 NM_002640.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19462013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB8	NM_002640.4	c.254T>C	p.Leu85Ser	missense_variant	Exon 3 of 7	ENST00000397985.7	NP_002631.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB8	ENST00000397985.7	c.254T>C	p.Leu85Ser	missense_variant	Exon 3 of 7	1	NM_002640.4	ENSP00000381072.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461756 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727188

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.0041	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	8.7
DANN	Benign	0.92
DEOGEN2	Benign	0.37	T;T;.;.;T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.30	.;T;T;T;T;T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.19	T;T;T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.97	L;L;.;L;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.4	N;N;.;D;N;D
REVEL	Benign	0.21
Sift	Benign	0.25	T;T;.;T;T;T
Sift4G	Benign	0.24	T;T;.;T;T;T
Polyphen		0.025	B;B;.;.;.;.
Vest4		0.054
MutPred		0.47		Gain of disorder (P = 0.0205);Gain of disorder (P = 0.0205);Gain of disorder (P = 0.0205);Gain of disorder (P = 0.0205);Gain of disorder (P = 0.0205);Gain of disorder (P = 0.0205);
MVP		0.69
MPC		0.046
ClinPred		0.17	T
GERP RS		3.6
Varity_R		0.14
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-61647120;