rs74511615

Variant names:

• chr9-105348387-C-A
• rs74511615
• NM_080546.5:c.436C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-105348387-C-A
• chr9-105348387-C-G
• chr9-105348387-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080546.5(SLC44A1):​c.436C>A​(p.Pro146Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P146S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC44A1 NM_080546.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.226096).

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.436C>A	p.Pro146Thr	missense	Exon 5 of 16	NP_536856.2
	SLC44A1	NM_001330731.2		c.436C>A	p.Pro146Thr	missense	Exon 5 of 16	NP_001317660.1	Q8WWI5-2
	SLC44A1	NM_001286730.2		c.436C>A	p.Pro146Thr	missense	Exon 5 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.436C>A	p.Pro146Thr	missense	Exon 5 of 16	ENSP00000363852.3	Q8WWI5-1
	SLC44A1	ENST00000374723.5	TSL:1	c.436C>A	p.Pro146Thr	missense	Exon 5 of 16	ENSP00000363855.1	Q8WWI5-3
	SLC44A1	ENST00000470972.5	TSL:1	n.436C>A		non_coding_transcript_exon	Exon 5 of 17	ENSP00000433072.1	Q8WWI5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458874 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 725890

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39558

South Asian (SAS) AF: 0.00 AC: 0 AN: 86112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109630

Other (OTH) AF: 0.00 AC: 0 AN: 60254

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.016
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.41
Sift	Benign	0.14	T
Sift4G	Benign	0.32	T
Polyphen		0.083	B
Vest4		0.33
MutPred		0.29		Loss of ubiquitination at K145 (P = 0.0585)
MVP		0.60
MPC		0.40
ClinPred		0.55	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.81
Mutation Taster		=64/36	polymorphism

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

dbSNP: rs74511615; hg19: chr9-108110668;