rs780272546

Variant names:

• chr14-94288518-C-T
• rs780272546
• NM_001100607.3:c.760G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-94288518-C-T
• chr14-94288518-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001100607.3(SERPINA10):​c.760G>A​(p.Asp254Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SERPINA10 NM_001100607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.32
• Publications: 0 publications found

Genes affected

SERPINA10 (HGNC:15996): (serpin family A member 10) The protein encoded by this gene belongs to the serpin family. It is predominantly expressed in the liver and secreted in plasma. It inhibits the activity of coagulation factors Xa and XIa in the presence of protein Z, calcium and phospholipid. Mutations in this gene are associated with venous thrombosis. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, May 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3314293).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100607.3. 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
	SERPINA10	NM_001100607.3	MANE Select	c.760G>A	p.Asp254Asn	missense	Exon 3 of 5	NP_001094077.1	Q9UK55
	SERPINA10	NM_016186.3		c.760G>A	p.Asp254Asn	missense	Exon 3 of 5	NP_057270.1	Q9UK55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA10	ENST00000261994.9	TSL:1 MANE Select	c.760G>A	p.Asp254Asn	missense	Exon 3 of 5	ENSP00000261994.4	Q9UK55
	SERPINA10	ENST00000554723.5	TSL:1	c.880G>A	p.Asp294Asn	missense	Exon 3 of 5	ENSP00000450896.1	G3V2W1
	SERPINA10	ENST00000393096.5	TSL:1	c.760G>A	p.Asp254Asn	missense	Exon 3 of 5	ENSP00000376809.1	Q9UK55

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251366 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727248

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: 0.0000232 AC: 2 AN: 86258

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: 8.99e-7 AC: 1 AN: 1112010

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

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	0.096
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.073
Eigen_PC	Benign	-0.025
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	0.086	D
MutationAssessor	Benign	1.9	L
PhyloP100		3.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.38
Sift	Benign	0.051	T
Sift4G	Benign	0.087	T
Polyphen		0.99	D
Vest4		0.15
MutPred		0.56		Loss of phosphorylation at T251 (P = 0.1)
MVP		0.75
MPC		0.19
ClinPred		0.87	D
GERP RS		3.4
Varity_R		0.49
gMVP		0.56
Mutation Taster		=76/24	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: rs780272546; hg19: chr14-94754855; COSMIC: COSV56227781;