rs371564737

Variant names:

• chr18-63639731-G-A
• rs371564737
• NM_002974.4:c.515C>T

Variant summary

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

The NM_002974.4(SERPINB4):​c.515C>T​(p.Thr172Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,610,942 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: SERPINB4 NM_002974.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.38
• Publications: 3 publications found

Genes affected

SERPINB4 (HGNC:10570): (serpin family B member 4) The protein encoded by this gene is a member of the serpin family of serine protease inhibitors. The encoded protein is highly expressed in many tumor cells and can inactivate granzyme M, an enzyme that kills tumor cells. This protein, along with serpin B3, can be processed into smaller fragments that aggregate to form an autoantigen in psoriasis, probably by causing chronic inflammation. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002974.4. 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
	SERPINB4	NM_002974.4	MANE Select	c.515C>T	p.Thr172Met	missense	Exon 6 of 8	NP_002965.1	P48594
	SERPINB4	NM_175041.2		c.515C>T	p.Thr172Met	missense	Exon 6 of 8	NP_778206.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB4	ENST00000341074.10	TSL:1 MANE Select	c.515C>T	p.Thr172Met	missense	Exon 6 of 8	ENSP00000343445.5	P48594
	SERPINB4	ENST00000413673.5	TSL:1	c.518C>T	p.Thr173Met	missense	Exon 5 of 7	ENSP00000398645.1	H0Y5H9
	SERPINB4	ENST00000436264.1	TSL:5	c.386C>T	p.Thr129Met	missense	Exon 5 of 6	ENSP00000399796.1	C9JZ65

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151994 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.0000399 AC: 10 AN: 250808 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0000871

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000192 AC: 28 AN: 1458948 Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13 AN XY: 725924

African (AFR) AF: 0.000270 AC: 9 AN: 33370

American (AMR) AF: 0.0000897 AC: 4 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26064

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39638

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000991 AC: 11 AN: 1109704

Other (OTH) AF: 0.00 AC: 0 AN: 60284

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151994 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74234

African (AFR) AF: 0.000121 AC: 5 AN: 41386

American (AMR) AF: 0.0000656 AC: 1 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000604

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000577 AC: 7

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Benign	0.15
Eigen_PC	Benign	-0.070
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.4
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.51
MVP		0.65
MPC		0.062
ClinPred		0.63	D
GERP RS		3.4
Varity_R		0.15
gMVP		0.64
Mutation Taster		=92/8	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: rs371564737; hg19: chr18-61306965; COSMIC: COSV61985475; COSMIC: COSV61985475;