rs2232710

Variant names:

• chr14-94284149-T-C
• rs2232710
• NM_001100607.3:c.1151A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001100607.3(SERPINA10):​c.1151A>G​(p.Gln384Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,613,922 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0078 (10 hom., cov: 32)
  • Exomes 𝑓: 0.010 (95 hom.)
• Consequence: SERPINA10 NM_001100607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37
• Publications: 15 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0077571273).
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA10	NM_001100607.3	MANE Select	c.1151A>G	p.Gln384Arg	missense	Exon 5 of 5	NP_001094077.1
	SERPINA10	NM_016186.3		c.1151A>G	p.Gln384Arg	missense	Exon 5 of 5	NP_057270.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA10	ENST00000261994.9	TSL:1 MANE Select	c.1151A>G	p.Gln384Arg	missense	Exon 5 of 5	ENSP00000261994.4
	SERPINA10	ENST00000554723.5	TSL:1	c.1271A>G	p.Gln424Arg	missense	Exon 5 of 5	ENSP00000450896.1
	SERPINA10	ENST00000393096.5	TSL:1	c.1151A>G	p.Gln384Arg	missense	Exon 5 of 5	ENSP00000376809.1

Frequencies

GnomAD3 genomes AF: 0.00782 AC: 1190 AN: 152246 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0230

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00806 AC: 2013 AN: 249768 AF XY: 0.00836

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0186

Gnomad NFE exome AF: 0.0120

Gnomad OTH exome AF: 0.00735

GnomAD4 exome AF: 0.0102 AC: 14960 AN: 1461558 Hom.: 95 Cov.: 32 AF XY: 0.00995 AC XY: 7232 AN XY: 727104

African (AFR) AF: 0.00158 AC: 53 AN: 33476

American (AMR) AF: 0.00293 AC: 131 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000727 AC: 19 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00348 AC: 300 AN: 86254

European-Finnish (FIN) AF: 0.0191 AC: 1020 AN: 53382

Middle Eastern (MID) AF: 0.0108 AC: 62 AN: 5764

European-Non Finnish (NFE) AF: 0.0116 AC: 12943 AN: 1111742

Other (OTH) AF: 0.00715 AC: 432 AN: 60392

GnomAD4 genome AF: 0.00781 AC: 1190 AN: 152364 Hom.: 10 Cov.: 32 AF XY: 0.00786 AC XY: 586 AN XY: 74510

African (AFR) AF: 0.00180 AC: 75 AN: 41588

American (AMR) AF: 0.00248 AC: 38 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

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

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4832

European-Finnish (FIN) AF: 0.0230 AC: 244 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0116 AC: 789 AN: 68028

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.0100 Hom.: 39

Bravo AF: 0.00643

TwinsUK AF: 0.0129 AC: 48

ALSPAC AF: 0.0104 AC: 40

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.0114 AC: 98

ExAC AF: 0.00823 AC: 999

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0118

EpiControl AF: 0.0103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	0.062
Eigen_PC	Benign	0.091
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0078	T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.4
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.40
Sift	Benign	0.13	T
Sift4G	Uncertain	0.051	T
Polyphen		0.23	B
Vest4		0.29
MVP		0.64
MPC		0.062
ClinPred		0.020	T
GERP RS		5.2
Varity_R		0.88
gMVP		0.75
Mutation Taster		=85/15	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: rs2232710; hg19: chr14-94750486; COSMIC: COSV108036645; COSMIC: COSV108036645;