NM_001100607.3:c.181A>G

Variant names:

• chr14-94290413-T-C
• rs941591
• NM_001100607.3:c.181A>G

Variant summary

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

The NM_001100607.3(SERPINA10):​c.181A>G​(p.Ser61Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,613,816 control chromosomes in the GnomAD database, including 37,756 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 0.25 (6045 hom., cov: 33)
  • Exomes 𝑓: 0.19 (31711 hom.)
• Consequence: SERPINA10 NM_001100607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.21
• Publications: 31 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=1.489452E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA10	NM_001100607.3	c.181A>G	p.Ser61Gly	missense_variant	Exon 2 of 5	ENST00000261994.9	NP_001094077.1
SERPINA10	NM_016186.3	c.181A>G	p.Ser61Gly	missense_variant	Exon 2 of 5		NP_057270.1
SERPINA10	XM_017021353.2	c.301A>G	p.Ser101Gly	missense_variant	Exon 3 of 6		XP_016876842.1
SERPINA10	XM_005267733.6	c.181A>G	p.Ser61Gly	missense_variant	Exon 2 of 5		XP_005267790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA10	ENST00000261994.9	c.181A>G	p.Ser61Gly	missense_variant	Exon 2 of 5	1	NM_001100607.3	ENSP00000261994.4
SERPINA10	ENST00000554723.5	c.301A>G	p.Ser101Gly	missense_variant	Exon 2 of 5	1		ENSP00000450896.1
SERPINA10	ENST00000393096.5	c.181A>G	p.Ser61Gly	missense_variant	Exon 2 of 5	1		ENSP00000376809.1
SERPINA10	ENST00000554173.1	c.181A>G	p.Ser61Gly	missense_variant	Exon 1 of 4	1		ENSP00000450971.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38297 AN: 152032 Hom.: 6025 Cov.: 33

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.234

GnomAD2 exomes AF: 0.227 AC: 56806 AN: 249708 AF XY: 0.223

Gnomad AFR exome AF: 0.412

Gnomad AMR exome AF: 0.169

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.587

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.191 AC: 278937 AN: 1461666 Hom.: 31711 Cov.: 37 AF XY: 0.192 AC XY: 139375 AN XY: 727112

African (AFR) AF: 0.422 AC: 14116 AN: 33480

American (AMR) AF: 0.171 AC: 7646 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 4511 AN: 26132

East Asian (EAS) AF: 0.587 AC: 23315 AN: 39694

South Asian (SAS) AF: 0.255 AC: 21974 AN: 86226

European-Finnish (FIN) AF: 0.188 AC: 10058 AN: 53384

Middle Eastern (MID) AF: 0.241 AC: 1388 AN: 5768

European-Non Finnish (NFE) AF: 0.164 AC: 182866 AN: 1111894

Other (OTH) AF: 0.216 AC: 13063 AN: 60382

GnomAD4 genome AF: 0.252 AC: 38368 AN: 152150 Hom.: 6045 Cov.: 33 AF XY: 0.254 AC XY: 18900 AN XY: 74384

African (AFR) AF: 0.405 AC: 16808 AN: 41502

American (AMR) AF: 0.170 AC: 2601 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3470

East Asian (EAS) AF: 0.589 AC: 3033 AN: 5150

South Asian (SAS) AF: 0.254 AC: 1225 AN: 4826

European-Finnish (FIN) AF: 0.206 AC: 2178 AN: 10590

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11177 AN: 67988

Other (OTH) AF: 0.233 AC: 492 AN: 2110

Alfa AF: 0.195 Hom.: 15608

Bravo AF: 0.259

TwinsUK AF: 0.156 AC: 579

ALSPAC AF: 0.167 AC: 645

ESP6500AA AF: 0.397 AC: 1748

ESP6500EA AF: 0.164 AC: 1414

ExAC AF: 0.231 AC: 28016

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.0060
DANN	Benign	0.15
DEOGEN2	Benign	0.045	T;.;T;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.27	.;T;T;.
MetaRNN	Benign	0.000015	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.34	N;.;N;N
PhyloP100		-4.2
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.27	N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.43	T;T;T;T
Sift4G	Benign	0.32	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.054
MPC		0.024
ClinPred		0.00083	T
GERP RS		-2.3
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.082
gMVP		0.27
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs941591; hg19: chr14-94756750; COSMIC: COSV56227746;