Variant 17-1766939-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002615.7(SERPINF1):c.29T>A(p.Ile10Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,413,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 7.1e-7 ( 0 hom. )

Consequence

SERPINF1
NM_002615.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.725

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14999554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SERPINF1	NM_002615.7 linkuse as main transcript	c.29T>A	p.Ile10Asn	missense_variant	2/8	ENST00000254722.9	NP_002606.3
SERPINF1	NM_001329903.2 linkuse as main transcript	c.29T>A	p.Ile10Asn	missense_variant	2/8		NP_001316832.1
SERPINF1	NM_001329904.2 linkuse as main transcript	c.-477-2913T>A		intron_variant			NP_001316833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9 linkuse as main transcript	c.29T>A	p.Ile10Asn	missense_variant	2/8	1	NM_002615.7	ENSP00000254722	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000114

AC:

AN:

175920

Hom.:

AF XY:

0.0000107

AC XY:

AN XY:

93680

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000750

Gnomad SAS exome

AF:

0.0000421

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1413362

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698520

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 29, 2024

The c.29T>A (p.I10N) alteration is located in exon 2 (coding exon 1) of the SERPINF1 gene. This alteration results from a T to A substitution at nucleotide position 29, causing the isoleucine (I) at amino acid position 10 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

0.0041

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.087

T;T;T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.74

T;T;T;T;T

M_CAP

Benign

0.070

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.0

N;.;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.83

N;.;.;.;.

REVEL

Benign

0.20

Sift

Benign

0.038

D;.;.;.;.

Sift4G

Uncertain

0.033

D;D;D;D;D

Polyphen

0.022

B;.;.;.;.

Vest4

0.39

MutPred

0.64

Gain of disorder (P = 0.0014);Gain of disorder (P = 0.0014);Gain of disorder (P = 0.0014);Gain of disorder (P = 0.0014);Gain of disorder (P = 0.0014);

MVP

0.46

MPC

0.12

ClinPred

0.053

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over