19-10632085-T-C

Variant names:

• chr19-10632085-T-C
• rs2067002774
• NM_020428.4:c.752T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020428.4(SLC44A2):​c.752T>C​(p.Ile251Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,894 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (1 hom.)
• Consequence: SLC44A2 NM_020428.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20607242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC44A2	NM_020428.4	c.752T>C	p.Ile251Thr	missense_variant	Exon 10 of 22	ENST00000335757.10	NP_065161.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC44A2	ENST00000335757.10	c.752T>C	p.Ile251Thr	missense_variant	Exon 10 of 22	1	NM_020428.4	ENSP00000336888.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461894 Hom.: 1 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.752T>C (p.I251T) alteration is located in exon 10 (coding exon 10) of the SLC44A2 gene. This alteration results from a T to C substitution at nucleotide position 752, causing the isoleucine (I) at amino acid position 251 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	.;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.0018
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;L;L
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.1	D;D;.
REVEL	Benign	0.13
Sift	Uncertain	0.014	D;D;.
Sift4G	Benign	0.11	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.32
MutPred		0.51		.;Loss of stability (P = 7e-04);Loss of stability (P = 7e-04);
MVP		0.32
MPC		0.41
ClinPred		0.64	D
GERP RS		3.9
Varity_R		0.13
gMVP		0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs2067002774; hg19: chr19-10742761;