6-2890501-C-T

Variant names:

• chr6-2890501-C-T
• rs372083827
• NM_004155.6:c.793G>A

Variant summary

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

The NM_004155.6(SERPINB9):​c.793G>A​(p.Val265Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V265F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: SERPINB9 NM_004155.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.906
• Publications: 0 publications found

Genes affected

SERPINB9 (HGNC:8955): (serpin family B member 9) This gene encodes a member of the serine protease inhibitor family which are also known as serpins. The encoded protein belongs to a subfamily of intracellular serpins. This protein inhibits the activity of the effector molecule granzyme B. Overexpression of this protein may prevent cytotoxic T-lymphocytes from eliminating certain tumor cells. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Mar 2012]

SERPINB9-AS1 (HGNC:56120): (SERPINB9 antisense RNA 1)

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=0.13478291).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004155.6. 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
	SERPINB9	NM_004155.6	MANE Select	c.793G>A	p.Val265Ile	missense	Exon 7 of 7	NP_004146.1	A0A024QZT4
	SERPINB9-AS1	NR_110841.1		n.224+5661C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB9	ENST00000380698.5	TSL:1 MANE Select	c.793G>A	p.Val265Ile	missense	Exon 7 of 7	ENSP00000370074.4	P50453
	SERPINB9	ENST00000718363.1		c.793G>A	p.Val265Ile	missense	Exon 7 of 7	ENSP00000520789.1	P50453
	SERPINB9	ENST00000893932.1		c.793G>A	p.Val265Ile	missense	Exon 8 of 8	ENSP00000563991.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.15
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.91
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.29
Sift	Benign	0.077	T
Sift4G	Benign	0.063	T
Polyphen		0.16	B
Vest4		0.10
MVP		0.67
MPC		0.11
ClinPred		0.38	T
GERP RS		3.8
Varity_R		0.065
gMVP		0.64
Mutation Taster		=94/6	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: rs372083827; hg19: chr6-2890735;