chr19-10631641-T-C

Variant names:

• chr19-10631641-T-C
• rs1253872880
• NM_020428.4:c.518T>C

Variant summary

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

The NM_020428.4(SLC44A2):​c.518T>C​(p.Phe173Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. F173C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC44A2 NM_020428.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.10
• Publications: 1 publications found

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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A2	NM_020428.4	MANE Select	c.518T>C	p.Phe173Ser	missense	Exon 8 of 22	NP_065161.3
	SLC44A2	NM_001363611.2		c.518T>C	p.Phe173Ser	missense	Exon 8 of 23	NP_001350540.1	Q8IWA5-2
	SLC44A2	NM_001145056.2		c.512T>C	p.Phe171Ser	missense	Exon 8 of 22	NP_001138528.1	A0A088QCU6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A2	ENST00000335757.10	TSL:1 MANE Select	c.518T>C	p.Phe173Ser	missense	Exon 8 of 22	ENSP00000336888.4	Q8IWA5-1
	SLC44A2	ENST00000407327.8	TSL:1	c.512T>C	p.Phe171Ser	missense	Exon 8 of 22	ENSP00000385135.3	Q8IWA5-3
	SLC44A2	ENST00000588465.5	TSL:1	n.427T>C		non_coding_transcript_exon	Exon 6 of 12

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 79

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		7.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.23	B
Vest4		0.73
MutPred		0.59		Gain of phosphorylation at F173 (P = 0.0535)
MVP		0.50
MPC		0.77
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.70
gMVP		0.94
Mutation Taster		=65/35	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: rs1253872880; hg19: chr19-10742317;