18-63903295-C-T

Variant names:

• chr18-63903295-C-T
• rs6104
• NM_002575.3:c.1238C>T

Variant summary

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

The NM_002575.3(SERPINB2):​c.1238C>T​(p.Ser413Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,376,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SERPINB2 NM_002575.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.933
• Publications: 0 publications found

Genes affected

SERPINB2 (HGNC:8584): (serpin family B member 2) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000289724 (HGNC:):

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=0.15231907).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002575.3. 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
	SERPINB2	NM_002575.3	MANE Select	c.1238C>T	p.Ser413Phe	missense	Exon 8 of 8	NP_002566.1	P05120
	SERPINB2	NM_001143818.2		c.1238C>T	p.Ser413Phe	missense	Exon 9 of 9	NP_001137290.1	P05120

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB2	ENST00000299502.9	TSL:1 MANE Select	c.1238C>T	p.Ser413Phe	missense	Exon 8 of 8	ENSP00000299502.4	P05120
	ENSG00000289724	ENST00000418725.1	TSL:5	c.546+320C>T		intron	N/A	ENSP00000392381.1	H7C004
	SERPINB2	ENST00000457692.5	TSL:5	c.1238C>T	p.Ser413Phe	missense	Exon 9 of 9	ENSP00000401645.1	P05120

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1376336 Hom.: 0 Cov.: 32 AF XY: 0.00000148 AC XY: 1 AN XY: 675540

African (AFR) AF: 0.00 AC: 0 AN: 30520

American (AMR) AF: 0.00 AC: 0 AN: 31784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20844

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38624

South Asian (SAS) AF: 0.00 AC: 0 AN: 71584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5346

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1070350

Other (OTH) AF: 0.00 AC: 0 AN: 56682

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.93
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.24
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.11	T
Polyphen		0.63	P
Vest4		0.14
MutPred		0.31		Loss of disorder (P = 0.011)
MVP		0.64
MPC		0.071
ClinPred		0.85	D
GERP RS		1.3
Varity_R		0.46
gMVP		0.18
Mutation Taster		=98/2	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: rs6104; hg19: chr18-61570529; COSMIC: COSV53075392; COSMIC: COSV53075392;