14-94446461-C-G

Variant names:

• chr14-94446461-C-G
• rs143678178
• NM_001080451.2:c.787G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001080451.2(SERPINA11):​c.787G>C​(p.Val263Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V263F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINA11 NM_001080451.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717
• Publications: 1 publications found

Genes affected

SERPINA11 (HGNC:19193): (serpin family A member 11) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SERPINA11 Gene-Disease associations (from GenCC):

• hydrops fetalis

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ENSG00000256357 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080451.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA11	NM_001080451.2	MANE Select	c.787G>C	p.Val263Leu	missense	Exon 3 of 5	NP_001073920.1	Q86U17
	SERPINA11	NM_001429948.1		c.175G>C	p.Val59Leu	missense	Exon 3 of 5	NP_001416877.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA11	ENST00000334708.4	TSL:1 MANE Select	c.787G>C	p.Val263Leu	missense	Exon 3 of 5	ENSP00000335024.3	Q86U17
	SERPINA11	ENST00000850861.1		c.796G>C	p.Val266Leu	missense	Exon 3 of 5	ENSP00000520948.1	A0ABJ7H2Z4
	SERPINA11	ENST00000905969.1		c.787G>C	p.Val263Leu	missense	Exon 3 of 5	ENSP00000576028.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251254 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.72	D
MutationAssessor	Benign	1.9	M
PhyloP100		0.72
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.42
Sift	Benign	0.096	T
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.17
MutPred		0.65		Loss of catalytic residue at E267 (P = 0.2207)
MVP		0.64
MPC		0.35
ClinPred		0.94	D
GERP RS		5.5
Varity_R		0.56
gMVP		0.50
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.31		Position offset: -9

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs143678178; hg19: chr14-94912798;