14-94446576-G-T

Variant names:

• chr14-94446576-G-T
• rs775643756
• NM_001080451.2:c.672C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_001080451.2(SERPINA11):​c.672C>A​(p.Tyr224*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINA11 NM_001080451.2 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.620

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]

ENSG00000256357 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-94446576-G-T is Pathogenic according to our data. Variant chr14-94446576-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 631492.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA11	NM_001080451.2	c.672C>A	p.Tyr224*	stop_gained	Exon 3 of 5	ENST00000334708.4	NP_001073920.1
SERPINA11	NM_001429948.1	c.60C>A	p.Tyr20*	stop_gained	Exon 3 of 5		NP_001416877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA11	ENST00000334708.4	c.672C>A	p.Tyr224*	stop_gained	Exon 3 of 5	1	NM_001080451.2	ENSP00000335024.3
ENSG00000256357	ENST00000536735.1	n.171+14835G>T		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pericardial effusion;C0032227:Pleural effusion Pathogenic:1

May 17, 2019

Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.14	N
Vest4		0.046
GERP RS		5.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.21		Position offset: 28

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

Publications

LitVar

Other links and lift over

dbSNP: rs775643756; hg19: chr14-94912913;