NM_001122752.2:c.251-98T>C

Variant names:

• chr3-167790274-T-C
• rs13090836
• NM_001122752.2:c.251-98T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001122752.2(SERPINI1):​c.251-98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 863,804 control chromosomes in the GnomAD database, including 71,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (16122 hom., cov: 32)
  • Exomes 𝑓: 0.39 (54890 hom.)
• Consequence: SERPINI1 NM_001122752.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.492
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-167790274-T-C is Benign according to our data. Variant chr3-167790274-T-C is described in ClinVar as Benign. ClinVar VariationId is 1230249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 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.251-98T>C		intron	N/A	NP_001116224.1	A0A0S2Z455
	SERPINI1	NM_005025.5		c.251-98T>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.251-98T>C		intron	N/A	ENSP00000397373.2	Q99574
	SERPINI1	ENST00000295777.9	TSL:1	c.251-98T>C		intron	N/A	ENSP00000295777.5	Q99574
	SERPINI1	ENST00000872947.1		c.251-98T>C		intron	N/A	ENSP00000543006.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67980 AN: 151924 Hom.: 16100 Cov.: 32

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.386 AC: 274509 AN: 711762 Hom.: 54890 AF XY: 0.378 AC XY: 142270 AN XY: 376098

African (AFR) AF: 0.602 AC: 11075 AN: 18402

American (AMR) AF: 0.330 AC: 12044 AN: 36516

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 4959 AN: 20532

East Asian (EAS) AF: 0.304 AC: 10413 AN: 34266

South Asian (SAS) AF: 0.261 AC: 17210 AN: 65840

European-Finnish (FIN) AF: 0.449 AC: 22563 AN: 50258

Middle Eastern (MID) AF: 0.284 AC: 782 AN: 2750

European-Non Finnish (NFE) AF: 0.406 AC: 181865 AN: 448008

Other (OTH) AF: 0.386 AC: 13598 AN: 35190

GnomAD4 genome AF: 0.448 AC: 68048 AN: 152042 Hom.: 16122 Cov.: 32 AF XY: 0.442 AC XY: 32864 AN XY: 74328

African (AFR) AF: 0.607 AC: 25153 AN: 41472

American (AMR) AF: 0.360 AC: 5503 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3470

East Asian (EAS) AF: 0.314 AC: 1621 AN: 5158

South Asian (SAS) AF: 0.256 AC: 1234 AN: 4826

European-Finnish (FIN) AF: 0.457 AC: 4823 AN: 10554

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27586 AN: 67964

Other (OTH) AF: 0.397 AC: 840 AN: 2116

Alfa AF: 0.479 Hom.: 7335

Bravo AF: 0.449

Asia WGS AF: 0.313 AC: 1089 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.36
PhyloP100		-0.49
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: rs13090836; hg19: chr3-167508062;