chr9-105335666-CTGAG-C

Position:

• chr9-105335666-CTGAG-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_080546.5(SLC44A1):​c.377_380delGTGA​(p.Ser126fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC44A1 NM_080546.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 4.44

Genes affected

SLC44A1 (HGNC:18798): (solute carrier family 44 member 1) Enables choline transmembrane transporter activity. Involved in choline transport and transmembrane transport. Located in several cellular components, including cytosol; mitochondrion; and nucleoplasm. Implicated in high grade glioma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-105335666-CTGAG-C is Pathogenic according to our data. Variant chr9-105335666-CTGAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 870503.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC44A1	NM_080546.5	c.377_380delGTGA	p.Ser126fs	frameshift_variant	4/16	ENST00000374720.8	NP_536856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC44A1	ENST00000374720.8	c.377_380delGTGA	p.Ser126fs	frameshift_variant	4/16	1	NM_080546.5	ENSP00000363852.3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline Pathogenic:2

Pathogenic, no assertion criteria provided	clinical testing	Institute of Human Genetics, University of Leipzig Medical Center	Mar 07, 2021	Review of the variants reported in Reuter et al., 2017, PMID: 28097321: PVS1,PM2 -
Pathogenic, no assertion criteria provided	literature only	OMIM	May 04, 2020	- -

Computational scores

Source: dbNSFP v4.3

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: rs1826893287; hg19: chr9-108097947;