chr3-167794834-T-C

Variant names:

• chr3-167794834-T-C
• rs113533056
• NM_001122752.2:c.881+10T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001122752.2(SERPINI1):​c.881+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,792 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SERPINI1 NM_001122752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17
• Publications: 0 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)

ENSG00000287319 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINI1	NM_001122752.2	c.881+10T>C		intron_variant	Intron 5 of 8	ENST00000446050.7	NP_001116224.1
SERPINI1	NM_005025.5	c.881+10T>C		intron_variant	Intron 5 of 8		NP_005016.1
SERPINI1	XM_017006618.3	c.881+10T>C		intron_variant	Intron 5 of 8		XP_016862107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINI1	ENST00000446050.7	c.881+10T>C		intron_variant	Intron 5 of 8	1	NM_001122752.2	ENSP00000397373.2
SERPINI1	ENST00000295777.9	c.881+10T>C		intron_variant	Intron 5 of 8	1		ENSP00000295777.5
SERPINI1	ENST00000472747.2	c.*155T>C		downstream_gene_variant		3		ENSP00000420561.2
ENSG00000287319	ENST00000661269.1	n.*113A>G		downstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458792 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725872

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110580

Other (OTH) AF: 0.00 AC: 0 AN: 60212

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.7
DANN	Benign	0.55
PhyloP100		3.2

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: rs113533056; hg19: chr3-167512622;