NM_001100607.3:c.1327C>G

Variant names:

• chr14-94283973-G-C
• rs1424048020
• NM_001100607.3:c.1327C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001100607.3(SERPINA10):​c.1327C>G​(p.Leu443Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SERPINA10 NM_001100607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058725417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA10	NM_001100607.3	c.1327C>G	p.Leu443Val	missense_variant	Exon 5 of 5	ENST00000261994.9	NP_001094077.1
SERPINA10	NM_016186.3	c.1327C>G	p.Leu443Val	missense_variant	Exon 5 of 5		NP_057270.1
SERPINA10	XM_017021353.2	c.1447C>G	p.Leu483Val	missense_variant	Exon 6 of 6		XP_016876842.1
SERPINA10	XM_005267733.6	c.1327C>G	p.Leu443Val	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.1327C>G	p.Leu443Val	missense_variant	Exon 5 of 5	1	NM_001100607.3	ENSP00000261994.4
SERPINA10	ENST00000554723.5	c.1447C>G	p.Leu483Val	missense_variant	Exon 5 of 5	1		ENSP00000450896.1
SERPINA10	ENST00000393096.5	c.1327C>G	p.Leu443Val	missense_variant	Exon 5 of 5	1		ENSP00000376809.1
SERPINA10	ENST00000554173.1	c.1327C>G	p.Leu443Val	missense_variant	Exon 4 of 4	1		ENSP00000450971.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461674 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	6.2
DANN	Benign	0.61
DEOGEN2	Benign	0.051	T;.;T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.50	.;T;T;.
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.059	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.97	L;.;L;L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.050	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.47	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0010	B;.;B;B
Vest4		0.076
MutPred		0.28		Gain of relative solvent accessibility (P = 0.0166);.;Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);
MVP		0.37
MPC		0.025
ClinPred		0.053	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs1424048020; hg19: chr14-94750310;