chr22-20779330-C-T

Position:

• chr22-20779330-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_000185.4(SERPIND1):​c.18C>T​(p.Asn6Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,210 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (30 hom.)
• Consequence: SERPIND1 NM_000185.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.687

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]

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 22-20779330-C-T is Benign according to our data. Variant chr22-20779330-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652915.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.687 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00127 (1857/1461886) while in subpopulation EAS AF= 0.0322 (1279/39700). AF 95% confidence interval is 0.0307. There are 30 homozygotes in gnomad4_exome. There are 957 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 144 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPIND1	NM_000185.4	c.18C>T	p.Asn6Asn	synonymous_variant	2/5	ENST00000215727.10	NP_000176.2
PI4KA	NM_058004.4	c.2329-13637G>A		intron_variant		ENST00000255882.11	NP_477352.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPIND1	ENST00000215727.10	c.18C>T	p.Asn6Asn	synonymous_variant	2/5	1	NM_000185.4	ENSP00000215727.5
PI4KA	ENST00000255882.11	c.2329-13637G>A		intron_variant		1	NM_058004.4	ENSP00000255882.6

Frequencies

GnomAD3 genomes AF: 0.000946 AC: 144 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000558

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00129 AC: 323 AN: 251336 Hom.: 0 AF XY: 0.00129 AC XY: 175 AN XY: 135850

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00198

Gnomad EAS exome AF: 0.00990

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.000730

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00127 AC: 1857 AN: 1461886 Hom.: 30 Cov.: 31 AF XY: 0.00132 AC XY: 957 AN XY: 727242

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00187

Gnomad4 EAS exome AF: 0.0322

Gnomad4 SAS exome AF: 0.0000927

Gnomad4 FIN exome AF: 0.000431

Gnomad4 NFE exome AF: 0.000387

Gnomad4 OTH exome AF: 0.000960

GnomAD4 genome AF: 0.000945 AC: 144 AN: 152324 Hom.: 1 Cov.: 32 AF XY: 0.000926 AC XY: 69 AN XY: 74484

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.0162

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000494 Hom.: 0

Bravo AF: 0.000808

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SERPIND1: BP4, BP7, BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.98
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs17819104; hg19: chr22-21133618;