14-94286221-G-A

Variant names:

• chr14-94286221-G-A
• rs149414832
• NM_001100607.3:c.1030C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001100607.3(SERPINA10):​c.1030C>T​(p.Gln344*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,820 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: 6.8e-7 (0 hom.)
• Consequence: SERPINA10 NM_001100607.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA10	NM_001100607.3	c.1030C>T	p.Gln344*	stop_gained	Exon 4 of 5	ENST00000261994.9	NP_001094077.1
SERPINA10	NM_016186.3	c.1030C>T	p.Gln344*	stop_gained	Exon 4 of 5		NP_057270.1
SERPINA10	XM_017021353.2	c.1150C>T	p.Gln384*	stop_gained	Exon 5 of 6		XP_016876842.1
SERPINA10	XM_005267733.6	c.1030C>T	p.Gln344*	stop_gained	Exon 4 of 5		XP_005267790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA10	ENST00000261994.9	c.1030C>T	p.Gln344*	stop_gained	Exon 4 of 5	1	NM_001100607.3	ENSP00000261994.4
SERPINA10	ENST00000554723.5	c.1150C>T	p.Gln384*	stop_gained	Exon 4 of 5	1		ENSP00000450896.1
SERPINA10	ENST00000393096.5	c.1030C>T	p.Gln344*	stop_gained	Exon 4 of 5	1		ENSP00000376809.1
SERPINA10	ENST00000554173.1	c.1030C>T	p.Gln344*	stop_gained	Exon 3 of 4	1		ENSP00000450971.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461820 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000159 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	37
DANN	Uncertain	0.98
Eigen	Uncertain	0.44
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.91	D
Vest4		0.89
GERP RS		3.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: 37

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: COSV104564503;