rs6797312

Variant names:

• chr3-167769515-A-T
• rs6797312
• NM_001122752.2:c.-18-19596A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001122752.2(SERPINI1):​c.-18-19596A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,012 control chromosomes in the GnomAD database, including 16,170 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16170 hom., cov: 32)
• Consequence: SERPINI1 NM_001122752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• progressive myoclonus epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• familial encephalopathy with neuroserpin inclusion bodies

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122752.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINI1	NM_001122752.2	MANE Select	c.-18-19596A>T		intron	N/A	NP_001116224.1	A0A0S2Z455
	SERPINI1	NM_005025.5		c.-18-19596A>T		intron	N/A	NP_005016.1	A0A0S2Z455

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINI1	ENST00000446050.7	TSL:1 MANE Select	c.-18-19596A>T		intron	N/A	ENSP00000397373.2	Q99574
	SERPINI1	ENST00000295777.9	TSL:1	c.-18-19596A>T		intron	N/A	ENSP00000295777.5	Q99574
	SERPINI1	ENST00000872947.1		c.-18-19596A>T		intron	N/A	ENSP00000543006.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68059 AN: 151894 Hom.: 16145 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.396

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.448 AC: 68128 AN: 152012 Hom.: 16170 Cov.: 32 AF XY: 0.443 AC XY: 32893 AN XY: 74300

African (AFR) AF: 0.609 AC: 25262 AN: 41466

American (AMR) AF: 0.359 AC: 5497 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3468

East Asian (EAS) AF: 0.314 AC: 1623 AN: 5176

South Asian (SAS) AF: 0.258 AC: 1243 AN: 4820

European-Finnish (FIN) AF: 0.456 AC: 4806 AN: 10532

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27571 AN: 67944

Other (OTH) AF: 0.396 AC: 835 AN: 2108

Alfa AF: 0.438 Hom.: 1877

Bravo AF: 0.450

Asia WGS AF: 0.313 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.8
DANN	Benign	0.66
PhyloP100		0.061
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6797312; hg19: chr3-167487303;