14-94286221-G-T

Position:

• chr14-94286221-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001100607.3(SERPINA10):​c.1030C>A​(p.Gln344Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SERPINA10 NM_001100607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29665738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA10	NM_001100607.3	c.1030C>A	p.Gln344Lys	missense_variant	4/5	ENST00000261994.9
SERPINA10	NM_016186.3	c.1030C>A	p.Gln344Lys	missense_variant	4/5
SERPINA10	XM_017021353.2	c.1150C>A	p.Gln384Lys	missense_variant	5/6
SERPINA10	XM_005267733.6	c.1030C>A	p.Gln344Lys	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA10	ENST00000261994.9	c.1030C>A	p.Gln344Lys	missense_variant	4/5	1	NM_001100607.3	A2
SERPINA10	ENST00000554723.5	c.1150C>A	p.Gln384Lys	missense_variant	4/5	1		P4
SERPINA10	ENST00000393096.5	c.1030C>A	p.Gln344Lys	missense_variant	4/5	1		A2
SERPINA10	ENST00000554173.1	c.1030C>A	p.Gln344Lys	missense_variant	3/4	1		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461820 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.1030C>A (p.Q344K) alteration is located in exon 4 (coding exon 3) of the SERPINA10 gene. This alteration results from a C to A substitution at nucleotide position 1030, causing the glutamine (Q) at amino acid position 344 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Benign	0.83
DEOGEN2	Benign	0.14	T;.;T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	.;T;T;.
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Uncertain	0.035	D
MutationAssessor	Benign	1.2	L;.;L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.036	D;T;D;D
Sift4G	Benign	0.063	T;T;T;T
Polyphen		0.96	D;.;D;D
Vest4		0.37
MutPred		0.43		Loss of ubiquitination at K345 (P = 0.0391);.;Loss of ubiquitination at K345 (P = 0.0391);Loss of ubiquitination at K345 (P = 0.0391);
MVP		0.49
MPC		0.14
ClinPred		0.89	D
GERP RS		3.5
Varity_R		0.67
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs149414832; hg19: chr14-94752558; COSMIC: COSV100003875;