19-10631490-C-T

Variant names:

• chr19-10631490-C-T
• rs147820753
• NM_020428.4:c.457C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_020428.4(SLC44A2):​c.457C>T​(p.Leu153Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,614,060 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L153I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0042 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (18 hom.)
• Consequence: SLC44A2 NM_020428.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.43
• Publications: 22 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039951503).
• BP6: Variant 19-10631490-C-T is Benign according to our data. Variant chr19-10631490-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2649298.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.457C>T	p.Leu153Phe	missense	Exon 7 of 22	NP_065161.3
	SLC44A2	NM_001363611.2		c.457C>T	p.Leu153Phe	missense	Exon 7 of 23	NP_001350540.1	Q8IWA5-2
	SLC44A2	NM_001145056.2		c.451C>T	p.Leu151Phe	missense	Exon 7 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.457C>T	p.Leu153Phe	missense	Exon 7 of 22	ENSP00000336888.4	Q8IWA5-1
	SLC44A2	ENST00000407327.8	TSL:1	c.451C>T	p.Leu151Phe	missense	Exon 7 of 22	ENSP00000385135.3	Q8IWA5-3
	SLC44A2	ENST00000588465.5	TSL:1	n.366C>T		non_coding_transcript_exon	Exon 5 of 12

Frequencies

GnomAD3 genomes AF: 0.00417 AC: 635 AN: 152138 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00700

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00430 AC: 1079 AN: 251190 AF XY: 0.00426

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00376

Gnomad ASJ exome AF: 0.00506

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00181

Gnomad NFE exome AF: 0.00664

Gnomad OTH exome AF: 0.00522

GnomAD4 exome AF: 0.00526 AC: 7695 AN: 1461804 Hom.: 18 Cov.: 38 AF XY: 0.00516 AC XY: 3750 AN XY: 727210

African (AFR) AF: 0.00119 AC: 40 AN: 33480

American (AMR) AF: 0.00378 AC: 169 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00601 AC: 157 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00169 AC: 146 AN: 86258

European-Finnish (FIN) AF: 0.00154 AC: 82 AN: 53344

Middle Eastern (MID) AF: 0.00485 AC: 28 AN: 5768

European-Non Finnish (NFE) AF: 0.00609 AC: 6776 AN: 1112000

Other (OTH) AF: 0.00490 AC: 296 AN: 60394

GnomAD4 genome AF: 0.00417 AC: 635 AN: 152256 Hom.: 3 Cov.: 32 AF XY: 0.00365 AC XY: 272 AN XY: 74440

African (AFR) AF: 0.00113 AC: 47 AN: 41562

American (AMR) AF: 0.00452 AC: 69 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00700 AC: 476 AN: 68010

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00473 Hom.: 2

Bravo AF: 0.00409

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00597 AC: 23

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00640 AC: 55

ExAC AF: 0.00431 AC: 523

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00731

EpiControl AF: 0.00670

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.096
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		3.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.13
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.072	T
Polyphen		0.15	B
Vest4		0.28
MVP		0.47
MPC		0.46
ClinPred		0.078	T
GERP RS		4.9
Varity_R		0.17
gMVP		0.83
Mutation Taster		=90/10	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: rs147820753; hg19: chr19-10742166; COSMIC: COSV100213425; COSMIC: COSV100213425;