NM_001122752.2:c.18C>T

Variant names:

• chr3-167789146-C-T
• rs752294814
• NM_001122752.2:c.18C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001122752.2(SERPINI1):​c.18C>T​(p.Leu6Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L6L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SERPINI1 NM_001122752.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• 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)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=-0.323 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINI1	NM_001122752.2	c.18C>T	p.Leu6Leu	synonymous_variant	Exon 2 of 9	ENST00000446050.7	NP_001116224.1
SERPINI1	NM_005025.5	c.18C>T	p.Leu6Leu	synonymous_variant	Exon 2 of 9		NP_005016.1
SERPINI1	XM_017006618.3	c.18C>T	p.Leu6Leu	synonymous_variant	Exon 2 of 9		XP_016862107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINI1	ENST00000446050.7	c.18C>T	p.Leu6Leu	synonymous_variant	Exon 2 of 9	1	NM_001122752.2	ENSP00000397373.2
SERPINI1	ENST00000295777.9	c.18C>T	p.Leu6Leu	synonymous_variant	Exon 2 of 9	1		ENSP00000295777.5
SERPINI1	ENST00000472747.2	c.18C>T	p.Leu6Leu	synonymous_variant	Exon 2 of 5	3		ENSP00000420561.2
SERPINI1	ENST00000472941.5	c.18C>T	p.Leu6Leu	synonymous_variant	Exon 2 of 3	3		ENSP00000420133.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	5.3
DANN	Benign	0.53
PhyloP100		-0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs752294814; hg19: chr3-167506934;