chr22-20779597-C-T

Position:

chr22-20779597-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_000185.4(SERPIND1):c.285C>T(p.Ile95Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00585 in 1,614,172 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 70 hom. )

Consequence

SERPIND1
NM_000185.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.754

Variant links:

Genes affected

SERPIND1 (HGNC:4838): (serpin family D member 1) This gene belongs to the serpin gene superfamily. Serpins play roles in many processes including inflammation, blood clotting, and cancer metastasis. Members of this family have highly conserved secondary structures with a reactive center loop that interacts with the protease active site to inhibit protease activity. This gene encodes a plasma serine protease that functions as a thrombin and chymotrypsin inhibitor. The protein is activated by heparin, dermatan sulfate, and glycosaminoglycans. Allelic variations in this gene are associated with heparin cofactor II deficiency. [provided by RefSeq, Jul 2015]

SERPIND1 links:

PI4KA (HGNC:8983): (phosphatidylinositol 4-kinase alpha) This gene encodes a phosphatidylinositol (PI) 4-kinase which catalyzes the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. The mammalian PI 4-kinases have been classified into two types, II and III, based on their molecular mass, and modulation by detergent and adenosine. The protein encoded by this gene is a type III enzyme that is not inhibited by adenosine. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2018]

PI4KA links:

PI4KA (HGNC:):

PI4KA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 22-20779597-C-T is Benign according to our data. Variant chr22-20779597-C-T is described in ClinVar as [Benign]. Clinvar id is 1269862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.754 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00586 (893/152358) while in subpopulation EAS AF= 0.0548 (284/5186). AF 95% confidence interval is 0.0495. There are 8 homozygotes in gnomad4. There are 420 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 893 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPIND1	NM_000185.4 linkuse as main transcript	c.285C>T	p.Ile95Ile	synonymous_variant	2/5	ENST00000215727.10	NP_000176.2	P05546Q8IVC0
PI4KA	NM_058004.4 linkuse as main transcript	c.2328+13596G>A		intron_variant		ENST00000255882.11	NP_477352.3	P42356-1Q4LE69B4DYG5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPIND1	ENST00000215727.10 linkuse as main transcript	c.285C>T	p.Ile95Ile	synonymous_variant	2/5	1	NM_000185.4	ENSP00000215727.5		P05546
PI4KA	ENST00000255882.11 linkuse as main transcript	c.2328+13596G>A		intron_variant		1	NM_058004.4	ENSP00000255882.6		P42356-1

Frequencies

GnomAD3 genomes

AF:

0.00589

AC:

897

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00765

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0550

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00522

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00741

AC:

1861

AN:

251062

Hom.:

AF XY:

0.00730

AC XY:

990

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00367

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0566

Gnomad SAS exome

AF:

0.00170

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00480

Gnomad OTH exome

AF:

0.00555

GnomAD4 exome

AF:

0.00585

AC:

8551

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00582

AC XY:

4229

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00376

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.0476

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.00520

Gnomad4 OTH exome

AF:

0.00634

GnomAD4 genome

AF:

0.00586

AC:

893

AN:

152358

Hom.:

Cov.:

AF XY:

0.00564

AC XY:

420

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00221

Gnomad4 AMR

AF:

0.00758

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0548

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00522

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00514

Hom.:

Bravo

AF:

0.00653

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.00502

EpiControl

AF:

0.00551

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 17, 2021	- -

SERPIND1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 14, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

6.4

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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