Variant 3-167789346-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001122752.2(SERPINI1):c.218G>T(p.Arg73Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SERPINI1
NM_001122752.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.94

Variant links:

Genes affected

SERPINI1 (HGNC:8943): (serpin family I member 1) This gene encodes a member of the serpin superfamily of serine proteinase inhibitors. The protein is primarily secreted by axons in the brain, and preferentially reacts with and inhibits tissue-type plasminogen activator. It is thought to play a role in the regulation of axonal growth and the development of synaptic plasticity. Mutations in this gene result in familial encephalopathy with neuroserpin inclusion bodies (FENIB), which is a dominantly inherited form of familial encephalopathy and epilepsy characterized by the accumulation of mutant neuroserpin polymers. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

SERPINI1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SERPINI1	NM_001122752.2 linkuse as main transcript	c.218G>T	p.Arg73Leu	missense_variant	2/9	ENST00000446050.7	NP_001116224.1
SERPINI1	NM_005025.5 linkuse as main transcript	c.218G>T	p.Arg73Leu	missense_variant	2/9		NP_005016.1
SERPINI1	XM_017006618.3 linkuse as main transcript	c.218G>T	p.Arg73Leu	missense_variant	2/9		XP_016862107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SERPINI1	ENST00000446050.7 linkuse as main transcript	c.218G>T	p.Arg73Leu	missense_variant	2/9	1	NM_001122752.2	ENSP00000397373	P1
SERPINI1	ENST00000295777.9 linkuse as main transcript	c.218G>T	p.Arg73Leu	missense_variant	2/9	1		ENSP00000295777	P1
SERPINI1	ENST00000472747.2 linkuse as main transcript	c.218G>T	p.Arg73Leu	missense_variant	2/5	3		ENSP00000420561
SERPINI1	ENST00000472941.5 linkuse as main transcript	c.218G>T	p.Arg73Leu	missense_variant	2/3	3		ENSP00000420133

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727202

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000194

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.92

D;.;D;D

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.63

D;D;D;D

MetaSVM

Uncertain

-0.087

MutationAssessor

Benign

1.1

.;L;L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Uncertain

0.58

Sift

Benign

0.054

T;T;T;T

Sift4G

Benign

0.34

T;T;T;T

Polyphen

1.0

.;D;D;.

Vest4

0.79

MutPred

0.49

Loss of phosphorylation at S75 (P = 0.0503);Loss of phosphorylation at S75 (P = 0.0503);Loss of phosphorylation at S75 (P = 0.0503);Loss of phosphorylation at S75 (P = 0.0503);

MVP

0.62

MPC

0.49

ClinPred

0.97

GERP RS

3.4

Varity_R

0.66

gMVP

0.74

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over