rs10513634

Positions:

• chr3-167809998-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000446050.7(SERPINI1):​c.979+2657T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,142 control chromosomes in the GnomAD database, including 1,077 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 0.11 (1077 hom., cov: 32)
• Consequence: SERPINI1 ENST00000446050.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINI1	NM_001122752.2	c.979+2657T>A		intron_variant		ENST00000446050.7	NP_001116224.1
SERPINI1	NM_005025.5	c.979+2657T>A		intron_variant			NP_005016.1
SERPINI1	XM_017006618.3	c.979+2657T>A		intron_variant			XP_016862107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINI1	ENST00000446050.7	c.979+2657T>A		intron_variant		1	NM_001122752.2	ENSP00000397373	P1
	ENST00000661269.1	n.545+539A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17248 AN: 152024 Hom.: 1079 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0899

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0229

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.113 AC: 17240 AN: 152142 Hom.: 1077 Cov.: 32 AF XY: 0.112 AC XY: 8361 AN XY: 74388

Gnomad4 AFR AF: 0.0832

Gnomad4 AMR AF: 0.0898

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0230

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.105

Alfa AF: 0.126 Hom.: 165

Bravo AF: 0.106

Asia WGS AF: 0.0850 AC: 295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs10513634; hg19: chr3-167527786;