chr3-167735251-T-C

Position:

• chr3-167735251-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000472941.5(SERPINI1):​c.-93T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,284 control chromosomes in the GnomAD database, including 26,532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (26503 hom., cov: 32)
  • Exomes 𝑓: 0.44 (29 hom.)
• Consequence: SERPINI1 ENST00000472941.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.84

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-167735251-T-C is Benign according to our data. Variant chr3-167735251-T-C is described in ClinVar as [Benign]. Clinvar id is 1168304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINI1	ENST00000472941.5	c.-93T>C		5_prime_UTR_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84830 AN: 151862 Hom.: 26447 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.438 AC: 133 AN: 304 Hom.: 29 Cov.: 0 AF XY: 0.448 AC XY: 104 AN XY: 232

Gnomad4 AFR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.786

GnomAD4 genome AF: 0.559 AC: 84924 AN: 151980 Hom.: 26503 Cov.: 32 AF XY: 0.550 AC XY: 40890 AN XY: 74280

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.462

Alfa AF: 0.527 Hom.: 2715

Bravo AF: 0.557

Asia WGS AF: 0.392 AC: 1366 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Familial encephalopathy with neuroserpin inclusion bodies Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.52
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9853967; hg19: chr3-167453039;