chr18-63589678-C-T

Variant names:

• chr18-63589678-C-T
• rs61733412
• NM_012397.4:c.188C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001348267.2(SERPINB13):​c.-214C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000249 in 1,613,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: SERPINB13 NM_001348267.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.159
• Publications: 8 publications found

Genes affected

SERPINB13 (HGNC:8944): (serpin family B member 13) The protein encoded by this gene is a member of the serpin family of serine protease inhibitors. The encoded protein inhibits the activity of cathepsin K and is itself transcriptionally repressed by RUNX1. This gene is downregulated in many types of cancer. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009098709).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348267.2. 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
	SERPINB13	NM_012397.4	MANE Select	c.188C>T	p.Thr63Met	missense	Exon 3 of 8	NP_036529.1	Q9UIV8-1
	SERPINB13	NM_001348267.2		c.-214C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	NP_001335196.1
	SERPINB13	NM_001348268.2		c.-431C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 9	NP_001335197.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB13	ENST00000344731.10	TSL:1 MANE Select	c.188C>T	p.Thr63Met	missense	Exon 3 of 8	ENSP00000341584.6	Q9UIV8-1
	SERPINB13	ENST00000269489.9	TSL:1	c.188C>T	p.Thr63Met	missense	Exon 3 of 8	ENSP00000269489.6	A0A0A0MQW3
	SERPINB13	ENST00000438844.1	TSL:1	n.188C>T		non_coding_transcript_exon	Exon 3 of 9	ENSP00000394592.1	F8WE70

Frequencies

GnomAD3 genomes AF: 0.000277 AC: 42 AN: 151752 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000509

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000243 AC: 61 AN: 250922 AF XY: 0.000243

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000246 AC: 359 AN: 1461360 Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 156 AN XY: 726964

African (AFR) AF: 0.000687 AC: 23 AN: 33466

American (AMR) AF: 0.000268 AC: 12 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00191 AC: 50 AN: 26130

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39588

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000229 AC: 255 AN: 1111678

Other (OTH) AF: 0.000149 AC: 9 AN: 60382

GnomAD4 genome AF: 0.000277 AC: 42 AN: 151868 Hom.: 0 Cov.: 32 AF XY: 0.000283 AC XY: 21 AN XY: 74186

African (AFR) AF: 0.000507 AC: 21 AN: 41384

American (AMR) AF: 0.0000656 AC: 1 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67978

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000482 Hom.: 0

Bravo AF: 0.000359

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000313 AC: 38

EpiCase AF: 0.000382

EpiControl AF: 0.000237

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	0.086
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	8.4
DANN	Benign	0.86
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0091	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.16
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.17
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.036	B
Vest4		0.20
MVP		0.53
MPC		0.032
ClinPred		0.042	T
GERP RS		-0.97
Varity_R		0.052
gMVP		0.18
Mutation Taster		=97/3	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: rs61733412; hg19: chr18-61256912; COSMIC: COSV54027286;