chr9-105299241-C-T

Variant names:

• chr9-105299241-C-T
• NM_080546.5:c.58C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_080546.5(SLC44A1):​c.58C>T​(p.Pro20Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC44A1 NM_080546.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.01
• Publications: 0 publications found

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]

SLC44A1 Gene-Disease associations (from GenCC):

• neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.803

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080546.5. 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
	SLC44A1	NM_080546.5	MANE Select	c.58C>T	p.Pro20Ser	missense	Exon 2 of 16	NP_536856.2
	SLC44A1	NM_001330731.2		c.58C>T	p.Pro20Ser	missense	Exon 2 of 16	NP_001317660.1	Q8WWI5-2
	SLC44A1	NM_001286730.2		c.58C>T	p.Pro20Ser	missense	Exon 2 of 16	NP_001273659.1	Q8WWI5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A1	ENST00000374720.8	TSL:1 MANE Select	c.58C>T	p.Pro20Ser	missense	Exon 2 of 16	ENSP00000363852.3	Q8WWI5-1
	SLC44A1	ENST00000374723.5	TSL:1	c.58C>T	p.Pro20Ser	missense	Exon 2 of 16	ENSP00000363855.1	Q8WWI5-3
	SLC44A1	ENST00000470972.5	TSL:1	n.58C>T		non_coding_transcript_exon	Exon 2 of 17	ENSP00000433072.1	Q8WWI5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1438346 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 715092

African (AFR) AF: 0.00 AC: 0 AN: 31838

American (AMR) AF: 0.00 AC: 0 AN: 39030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25520

East Asian (EAS) AF: 0.00 AC: 0 AN: 38244

South Asian (SAS) AF: 0.00 AC: 0 AN: 81760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5342

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103932

Other (OTH) AF: 0.00 AC: 0 AN: 59508

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.46		Loss of catalytic residue at P20 (P = 0.0226)
MVP		0.66
MPC		1.1
ClinPred		0.99	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.47
gMVP		0.81
Mutation Taster		=43/57	disease causing

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

hg19: chr9-108061522;