rs6783981

Variant names:

• chr3-167810341-T-C
• rs6783981
• NM_001122752.2:c.979+3000T>C

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+3000T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,844 control chromosomes in the GnomAD database, including 24,492 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 0.54 (24492 hom., cov: 31)
• Consequence: SERPINI1 NM_001122752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 10 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000287319 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 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.979+3000T>C		intron	N/A	NP_001116224.1	A0A0S2Z455
	SERPINI1	NM_005025.5		c.979+3000T>C		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.979+3000T>C		intron	N/A	ENSP00000397373.2	Q99574
	SERPINI1	ENST00000295777.9	TSL:1	c.979+3000T>C		intron	N/A	ENSP00000295777.5	Q99574
	SERPINI1	ENST00000872947.1		c.979+3000T>C		intron	N/A	ENSP00000543006.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82456 AN: 151726 Hom.: 24459 Cov.: 31

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.544 AC: 82535 AN: 151844 Hom.: 24492 Cov.: 31 AF XY: 0.532 AC XY: 39460 AN XY: 74196

African (AFR) AF: 0.756 AC: 31321 AN: 41416

American (AMR) AF: 0.425 AC: 6480 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1639 AN: 3470

East Asian (EAS) AF: 0.0745 AC: 386 AN: 5178

South Asian (SAS) AF: 0.289 AC: 1387 AN: 4806

European-Finnish (FIN) AF: 0.468 AC: 4920 AN: 10520

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.512 AC: 34761 AN: 67896

Other (OTH) AF: 0.528 AC: 1115 AN: 2112

Alfa AF: 0.510 Hom.: 12830

Bravo AF: 0.551

Asia WGS AF: 0.232 AC: 806 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		1.3
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: rs6783981; hg19: chr3-167528129;