14-94288467-C-T

Variant names:

• chr14-94288467-C-T
• rs2232708
• NM_001100607.3:c.811G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100607.3(SERPINA10):​c.811G>A​(p.Gly271Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,614,006 control chromosomes in the GnomAD database, including 448 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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: 𝑓 0.031 (198 hom., cov: 32)
  • Exomes 𝑓: 0.0094 (250 hom.)
• Consequence: SERPINA10 NM_001100607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016829967).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA10	NM_001100607.3	c.811G>A	p.Gly271Ser	missense_variant	Exon 3 of 5	ENST00000261994.9	NP_001094077.1
SERPINA10	NM_016186.3	c.811G>A	p.Gly271Ser	missense_variant	Exon 3 of 5		NP_057270.1
SERPINA10	XM_017021353.2	c.931G>A	p.Gly311Ser	missense_variant	Exon 4 of 6		XP_016876842.1
SERPINA10	XM_005267733.6	c.811G>A	p.Gly271Ser	missense_variant	Exon 3 of 5		XP_005267790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA10	ENST00000261994.9	c.811G>A	p.Gly271Ser	missense_variant	Exon 3 of 5	1	NM_001100607.3	ENSP00000261994.4
SERPINA10	ENST00000554723.5	c.931G>A	p.Gly311Ser	missense_variant	Exon 3 of 5	1		ENSP00000450896.1
SERPINA10	ENST00000393096.5	c.811G>A	p.Gly271Ser	missense_variant	Exon 3 of 5	1		ENSP00000376809.1
SERPINA10	ENST00000554173.1	c.811G>A	p.Gly271Ser	missense_variant	Exon 2 of 4	1		ENSP00000450971.1

Frequencies

GnomAD3 genomes AF: 0.0307 AC: 4665 AN: 152000 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.00654

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.0142 AC: 3577 AN: 251456 AF XY: 0.0131

Gnomad AFR exome AF: 0.0920

Gnomad AMR exome AF: 0.0123

Gnomad ASJ exome AF: 0.0259

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00692

Gnomad OTH exome AF: 0.0164

GnomAD4 exome AF: 0.00940 AC: 13735 AN: 1461888 Hom.: 250 Cov.: 32 AF XY: 0.00947 AC XY: 6890 AN XY: 727246

African (AFR) AF: 0.0927 AC: 3102 AN: 33478

American (AMR) AF: 0.0124 AC: 555 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 728 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0162 AC: 1397 AN: 86258

European-Finnish (FIN) AF: 0.00150 AC: 80 AN: 53420

Middle Eastern (MID) AF: 0.0744 AC: 429 AN: 5768

European-Non Finnish (NFE) AF: 0.00584 AC: 6497 AN: 1112010

Other (OTH) AF: 0.0156 AC: 943 AN: 60394

GnomAD4 genome AF: 0.0307 AC: 4668 AN: 152118 Hom.: 198 Cov.: 32 AF XY: 0.0299 AC XY: 2223 AN XY: 74358

African (AFR) AF: 0.0897 AC: 3720 AN: 41472

American (AMR) AF: 0.0161 AC: 246 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 100 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0144 AC: 69 AN: 4808

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10600

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.00654 AC: 445 AN: 67996

Other (OTH) AF: 0.0242 AC: 51 AN: 2110

Alfa AF: 0.0166 Hom.: 120

Bravo AF: 0.0340

TwinsUK AF: 0.00836 AC: 31

ALSPAC AF: 0.00597 AC: 23

ESP6500AA AF: 0.0865 AC: 381

ESP6500EA AF: 0.00814 AC: 70

ExAC AF: 0.0161 AC: 1954

Asia WGS AF: 0.0120 AC: 44 AN: 3478

EpiCase AF: 0.0110

EpiControl AF: 0.00972

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.66
DEOGEN2	Benign	0.099	T;.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0078	N
LIST_S2	Benign	0.36	.;T;T;.
MetaRNN	Benign	0.0017	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.3	N;.;N;N
PhyloP100		0.44
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.3	N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.24	T;T;T;T
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.11	B;.;B;B
Vest4		0.018
MPC		0.028
ClinPred		0.0027	T
GERP RS		-2.3
Varity_R		0.20
gMVP		0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2232708; hg19: chr14-94754804; COSMIC: COSV104564490;