3-167813232-C-T

Variant names:

• chr3-167813232-C-T
• rs1552746
• NM_001122752.2:c.979+5891C>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.979+5891C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,144 control chromosomes in the GnomAD database, including 49,859 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 0.81 (49859 hom., cov: 32)
• Consequence: SERPINI1 NM_001122752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 3 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, 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINI1	NM_001122752.2	MANE Select	c.979+5891C>T		intron	N/A	NP_001116224.1
	SERPINI1	NM_005025.5		c.979+5891C>T		intron	N/A	NP_005016.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINI1	ENST00000446050.7	TSL:1 MANE Select	c.979+5891C>T		intron	N/A	ENSP00000397373.2
	SERPINI1	ENST00000295777.9	TSL:1	c.979+5891C>T		intron	N/A	ENSP00000295777.5
	SERPINI1	ENST00000466865.1	TSL:2	c.103+5891C>T		intron	N/A	ENSP00000420807.1

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122814 AN: 152026 Hom.: 49818 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.832

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

GnomAD4 genome AF: 0.808 AC: 122910 AN: 152144 Hom.: 49859 Cov.: 32 AF XY: 0.809 AC XY: 60192 AN XY: 74376

African (AFR) AF: 0.750 AC: 31124 AN: 41474

American (AMR) AF: 0.874 AC: 13360 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2716 AN: 3472

East Asian (EAS) AF: 0.966 AC: 5001 AN: 5178

South Asian (SAS) AF: 0.860 AC: 4150 AN: 4826

European-Finnish (FIN) AF: 0.808 AC: 8563 AN: 10600

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55297 AN: 67996

Other (OTH) AF: 0.833 AC: 1760 AN: 2112

Alfa AF: 0.810 Hom.: 6201

Bravo AF: 0.811

Asia WGS AF: 0.891 AC: 3098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.28
DANN	Benign	0.39
PhyloP100		-1.4
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: rs1552746; hg19: chr3-167531020;