17-1777321-C-T

Position:

• chr17-1777321-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

The NM_002615.7(SERPINF1):​c.1132C>T​(p.Gln378*) 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SERPINF1 NM_002615.7 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 1.13

Genes affected

SERPINF1 (HGNC:8824): (serpin family F member 1) This gene encodes a member of the serpin family that does not display the serine protease inhibitory activity shown by many of the other serpin proteins. The encoded protein is secreted and strongly inhibits angiogenesis. In addition, this protein is a neurotrophic factor involved in neuronal differentiation in retinoblastoma cells. Mutations in this gene were found in individuals with osteogenesis imperfecta, type VI. [provided by RefSeq, Aug 2016]

SERPINF1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0994 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-1777321-C-T is Pathogenic according to our data. Variant chr17-1777321-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 31853.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINF1	NM_002615.7	c.1132C>T	p.Gln378*	stop_gained	8/8	ENST00000254722.9	NP_002606.3
SERPINF1	NM_001329903.2	c.1132C>T	p.Gln378*	stop_gained	8/8		NP_001316832.1
SERPINF1	NM_001329904.2	c.571C>T	p.Gln191*	stop_gained	7/7		NP_001316833.1
SERPINF1	NM_001329905.2	c.571C>T	p.Gln191*	stop_gained	4/4		NP_001316834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9	c.1132C>T	p.Gln378*	stop_gained	8/8	1	NM_002615.7	ENSP00000254722.4
SERPINF1	ENST00000572517.1	n.428C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Osteogenesis imperfecta type 6 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 11, 2011

- -

not provided Other:1

not provided, no classification provided

curation

Osteogenesis Imperfecta Variant Database (SERPINF1)

Mar 02, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.81	D
Vest4		0.77
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs193302873; hg19: chr17-1680615;