rs775643756

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-94446576-G-T
• chr14-94446576-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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 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 VariationId is 631492.Status of the report is criteria_provided_single_submitter, 1 stars.

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.672C>A	p.Tyr224*	stop_gained	Exon 3 of 5	NP_001073920.1	Q86U17
	SERPINA11	NM_001429948.1		c.60C>A	p.Tyr20*	stop_gained	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.672C>A	p.Tyr224*	stop_gained	Exon 3 of 5	ENSP00000335024.3	Q86U17
	SERPINA11	ENST00000850861.1		c.681C>A	p.Tyr227*	stop_gained	Exon 3 of 5	ENSP00000520948.1	A0ABJ7H2Z4
	SERPINA11	ENST00000905969.1		c.672C>A	p.Tyr224*	stop_gained	Exon 3 of 5	ENSP00000576028.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Pericardial effusion;C0032227:Pleural effusion (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.62
Vest4		0.046
GERP RS		5.4
Mutation Taster		=44/156	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs775643756; hg19: chr14-94912913;