rs766735149

Variant names:

• chr19-10625638-G-A
• rs766735149
• NM_020428.4:c.5G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-10625638-G-A
• chr19-10625638-G-T

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.5G>A​(p.Gly2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,248,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: SLC44A2 NM_020428.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.05
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12694576).

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.5G>A	p.Gly2Glu	missense	Exon 1 of 22	NP_065161.3
	SLC44A2	NM_001363611.2		c.5G>A	p.Gly2Glu	missense	Exon 1 of 23	NP_001350540.1	Q8IWA5-2
	SLC44A2	NM_001145056.2		c.32-615G>A		intron	N/A	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.5G>A	p.Gly2Glu	missense	Exon 1 of 22	ENSP00000336888.4	Q8IWA5-1
	SLC44A2	ENST00000407327.8	TSL:1	c.32-615G>A		intron	N/A	ENSP00000385135.3	Q8IWA5-3
	SLC44A2	ENST00000588465.5	TSL:1	n.106-615G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152100 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 11380 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000456 AC: 5 AN: 1096360 Hom.: 0 Cov.: 31 AF XY: 0.00000385 AC XY: 2 AN XY: 518984

African (AFR) AF: 0.00 AC: 0 AN: 23012

American (AMR) AF: 0.00 AC: 0 AN: 8552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14422

East Asian (EAS) AF: 0.00 AC: 0 AN: 26574

South Asian (SAS) AF: 0.00 AC: 0 AN: 21706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.00000542 AC: 5 AN: 923162

Other (OTH) AF: 0.00 AC: 0 AN: 44034

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152100 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74288

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000615 AC: 1

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	0.073
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.0
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.12
Sift	Benign	0.21	T
Sift4G	Benign	0.16	T
Polyphen		0.0010	B
Vest4		0.31
MutPred		0.19		Gain of solvent accessibility (P = 0.024)
MVP		0.43
MPC		0.43
ClinPred		0.55	D
GERP RS		4.2
PromoterAI		0.082	Neutral
Varity_R		0.11
gMVP		0.48
Mutation Taster		=93/7	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: rs766735149; hg19: chr19-10736314;