rs190358836

Variant names:

• chr14-94284047-C-A
• NM_001100607.3:c.1253G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-94284047-C-A
• chr14-94284047-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001100607.3(SERPINA10):​c.1253G>T​(p.Arg418Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SERPINA10 NM_001100607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.872

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.962

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA10	NM_001100607.3	c.1253G>T	p.Arg418Leu	missense_variant	Exon 5 of 5	ENST00000261994.9	NP_001094077.1
SERPINA10	NM_016186.3	c.1253G>T	p.Arg418Leu	missense_variant	Exon 5 of 5		NP_057270.1
SERPINA10	XM_017021353.2	c.1373G>T	p.Arg458Leu	missense_variant	Exon 6 of 6		XP_016876842.1
SERPINA10	XM_005267733.6	c.1253G>T	p.Arg418Leu	missense_variant	Exon 5 of 5		XP_005267790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA10	ENST00000261994.9	c.1253G>T	p.Arg418Leu	missense_variant	Exon 5 of 5	1	NM_001100607.3	ENSP00000261994.4
SERPINA10	ENST00000554723.5	c.1373G>T	p.Arg458Leu	missense_variant	Exon 5 of 5	1		ENSP00000450896.1
SERPINA10	ENST00000393096.5	c.1253G>T	p.Arg418Leu	missense_variant	Exon 5 of 5	1		ENSP00000376809.1
SERPINA10	ENST00000554173.1	c.1253G>T	p.Arg418Leu	missense_variant	Exon 4 of 4	1		ENSP00000450971.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461880 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D;.;D;D
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.81	.;T;T;.
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.96	D;D;D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Pathogenic	3.7	H;.;H;H
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-5.7	D;D;D;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.024	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.60
MutPred		0.83		Gain of catalytic residue at F422 (P = 0.1737);.;Gain of catalytic residue at F422 (P = 0.1737);Gain of catalytic residue at F422 (P = 0.1737);
MVP		0.64
MPC		0.22
ClinPred		0.98	D
GERP RS		-1.3
Varity_R		0.79
gMVP		0.76

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-94750384;