chr19-10625638-G-T

Variant names:

• chr19-10625638-G-T
• rs766735149
• NM_020428.4:c.5G>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>T​(p.Gly2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. G2E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: SLC44A2 NM_020428.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05
• 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=0.18154162).

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>T	p.Gly2Val	missense	Exon 1 of 22	NP_065161.3
	SLC44A2	NM_001363611.2		c.5G>T	p.Gly2Val	missense	Exon 1 of 23	NP_001350540.1	Q8IWA5-2
	SLC44A2	NM_001145056.2		c.32-615G>T		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>T	p.Gly2Val	missense	Exon 1 of 22	ENSP00000336888.4	Q8IWA5-1
	SLC44A2	ENST00000407327.8	TSL:1	c.32-615G>T		intron	N/A	ENSP00000385135.3	Q8IWA5-3
	SLC44A2	ENST00000588465.5	TSL:1	n.106-615G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096360 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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: 0.00000108 AC: 1 AN: 923162

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.0
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.13
Sift	Benign	0.041	D
Sift4G	Uncertain	0.015	D
Polyphen		0.0020	B
Vest4		0.33
MutPred		0.19		Gain of solvent accessibility (P = 0.1133)
MVP		0.52
MPC		0.41
ClinPred		0.80	D
GERP RS		4.2
PromoterAI		0.095	Neutral
Varity_R		0.17
gMVP		0.51
Mutation Taster		=91/9	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;