NM_020428.4:c.40A>G

Variant names:

• chr19-10626255-A-G
• NM_020428.4:c.40A>G

Variant summary

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

The NM_020428.4(SLC44A2):​c.40A>G​(p.Thr14Ala) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC44A2 NM_020428.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15803552).

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.40A>G	p.Thr14Ala	missense splice_region	Exon 2 of 22	NP_065161.3
	SLC44A2	NM_001363611.2		c.40A>G	p.Thr14Ala	missense splice_region	Exon 2 of 23	NP_001350540.1	Q8IWA5-2
	SLC44A2	NM_001145056.2		c.34A>G	p.Thr12Ala	missense splice_region	Exon 2 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.40A>G	p.Thr14Ala	missense splice_region	Exon 2 of 22	ENSP00000336888.4	Q8IWA5-1
	SLC44A2	ENST00000407327.8	TSL:1	c.34A>G	p.Thr12Ala	missense splice_region	Exon 2 of 22	ENSP00000385135.3	Q8IWA5-3
	SLC44A2	ENST00000588465.5	TSL:1	n.108A>G		splice_region non_coding_transcript_exon	Exon 2 of 12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	Benign	0.069
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.062
Sift	Benign	0.15	T
Sift4G	Benign	0.20	T
Polyphen		0.0040	B
Vest4		0.21
MutPred		0.21		Loss of phosphorylation at T14 (P = 0.0111)
MVP		0.40
MPC		0.33
ClinPred		0.54	D
GERP RS		4.1
Varity_R		0.033
gMVP		0.52
Mutation Taster		=81/19	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

hg19: chr19-10736931;