14-94290320-T-A

Position:

• chr14-94290320-T-A

Variant summary

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

The NM_001100607.3(SERPINA10):​c.274A>T​(p.Met92Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SERPINA10 NM_001100607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.302

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=0.049610734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA10	NM_001100607.3	c.274A>T	p.Met92Leu	missense_variant	2/5	ENST00000261994.9
SERPINA10	NM_016186.3	c.274A>T	p.Met92Leu	missense_variant	2/5
SERPINA10	XM_017021353.2	c.394A>T	p.Met132Leu	missense_variant	3/6
SERPINA10	XM_005267733.6	c.274A>T	p.Met92Leu	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA10	ENST00000261994.9	c.274A>T	p.Met92Leu	missense_variant	2/5	1	NM_001100607.3	A2
SERPINA10	ENST00000554723.5	c.394A>T	p.Met132Leu	missense_variant	2/5	1		P4
SERPINA10	ENST00000393096.5	c.274A>T	p.Met92Leu	missense_variant	2/5	1		A2
SERPINA10	ENST00000554173.1	c.274A>T	p.Met92Leu	missense_variant	1/4	1		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

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

Oct 12, 2022

The c.274A>T (p.M92L) alteration is located in exon 2 (coding exon 1) of the SERPINA10 gene. This alteration results from a A to T substitution at nucleotide position 274, causing the methionine (M) at amino acid position 92 to be replaced by a leucine (L). 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	0.083
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	1.9
DANN	Benign	0.59
DEOGEN2	Benign	0.13	T;.;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.19	N
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.050	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.095	N;.;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.097	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0020	B;.;B;B
Vest4		0.22
MutPred		0.36		Loss of MoRF binding (P = 0.0769);.;Loss of MoRF binding (P = 0.0769);Loss of MoRF binding (P = 0.0769);
MVP		0.13
MPC		0.025
ClinPred		0.031	T
GERP RS		-3.0
Varity_R		0.38
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-94756657;