Genetic Variant NM_002615.7:c.73C>A (chr17-1766983-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002615.7(SERPINF1):c.73C>A(p.Pro25Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000356 in 1,402,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

SERPINF1
NM_002615.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.506

Publications

0 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

osteogenesis imperfecta type 6
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
osteogenesis imperfecta type 3
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
osteogenesis imperfecta type 4
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SERPINF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05766478).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002615.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINF1	NM_002615.7	MANE Select	c.73C>A	p.Pro25Thr	missense	Exon 2 of 8	NP_002606.3
SERPINF1	NM_001329903.2		c.73C>A	p.Pro25Thr	missense	Exon 2 of 8	NP_001316832.1	A0A140VKF3
SERPINF1	NM_001329904.2		c.-477-2869C>A		intron	N/A	NP_001316833.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINF1	ENST00000254722.9	TSL:1 MANE Select	c.73C>A	p.Pro25Thr	missense	Exon 2 of 8	ENSP00000254722.4	P36955
SERPINF1	ENST00000869424.1		c.73C>A	p.Pro25Thr	missense	Exon 2 of 8	ENSP00000539483.1
SERPINF1	ENST00000869426.1		c.73C>A	p.Pro25Thr	missense	Exon 2 of 8	ENSP00000539485.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000628

AC:

AN:

159216

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000161

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000356

AC:

AN:

1402928

Hom.:

Cov.:

AF XY:

0.00000578

AC XY:

AN XY:

692336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31904

American (AMR)

AF:

0.00

AC:

AN:

36142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25188

East Asian (EAS)

AF:

0.00

AC:

AN:

36274

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79470

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5486

European-Non Finnish (NFE)

AF:

0.00000370

AC:

AN:

1081048

Other (OTH)

AF:

0.00

AC:

AN:

58100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.020

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.041

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00088

LIST_S2

Benign

0.35

M_CAP

Benign

0.056

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.0

PhyloP100

-0.51

PrimateAI

Benign

0.31

PROVEAN

Benign

0.080

REVEL

Benign

0.23

Sift

Benign

0.76

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.11

MutPred

0.29

Loss of catalytic residue at P25 (P = 4e-04)

MVP

0.60

MPC

0.073

ClinPred

0.013

GERP RS

-5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.041

gMVP

0.31

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over