Genetic Variant SLC44A2:p.Phe173Cys (chr19-10631641-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_020428.4(SLC44A2):c.518T>G(p.Phe173Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,464 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC44A2
NM_020428.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.10

Publications

1 publications found

Variant links:

Genes affected

SLC44A2 (HGNC:17292): (solute carrier family 44 member 2 (CTL2 blood group)) Enables choline transmembrane transporter activity. Involved in choline transport and transmembrane transport. Located in mitochondrion and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC44A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020428.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC44A2	NM_020428.4	MANE Select	c.518T>G	p.Phe173Cys	missense	Exon 8 of 22	NP_065161.3
SLC44A2	NM_001363611.2		c.518T>G	p.Phe173Cys	missense	Exon 8 of 23	NP_001350540.1	Q8IWA5-2
SLC44A2	NM_001145056.2		c.512T>G	p.Phe171Cys	missense	Exon 8 of 22	NP_001138528.1	A0A088QCU6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC44A2	ENST00000335757.10	TSL:1 MANE Select	c.518T>G	p.Phe173Cys	missense	Exon 8 of 22	ENSP00000336888.4	Q8IWA5-1
SLC44A2	ENST00000407327.8	TSL:1	c.512T>G	p.Phe171Cys	missense	Exon 8 of 22	ENSP00000385135.3	Q8IWA5-3
SLC44A2	ENST00000588465.5	TSL:1	n.427T>G		non_coding_transcript_exon	Exon 6 of 12

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250502

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461464

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727030

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53038

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111986

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.0076

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Pathogenic

0.68

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.2

PhyloP100

7.1

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-4.2

REVEL

Uncertain

0.31

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.98

Vest4

0.66

MutPred

0.38

Gain of helix (P = 0.132)

MVP

0.58

MPC

1.0

ClinPred

0.99

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.47

gMVP

0.93

Mutation Taster

=60/40

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over