rs7944051

Variant names:

• chr11-62888346-C-T
• rs7944051
• NM_001013251.3:c.1243C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001013251.3(SLC3A2):​c.1243C>T​(p.Pro415Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000783 in 1,613,958 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (7 hom.)
• Consequence: SLC3A2 NM_001013251.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.178
• Publications: 5 publications found

Genes affected

SLC3A2 (HGNC:11026): (solute carrier family 3 member 2) This gene is a member of the solute carrier family and encodes a cell surface, transmembrane protein. The protein exists as the heavy chain of a heterodimer, covalently bound through di-sulfide bonds to one of several possible light chains. The encoded transporter plays a role in regulation of intracellular calcium levels and transports L-type amino acids. Alternatively spliced transcript variants, encoding different isoforms, have been characterized. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050282776).
• BP6: Variant 11-62888346-C-T is Benign according to our data. Variant chr11-62888346-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 789487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 600 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013251.3. 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
	SLC3A2	NM_001013251.3	MANE Select	c.1243C>T	p.Pro415Ser	missense	Exon 9 of 9	NP_001013269.1	P08195-2
	SLC3A2	NM_001012662.3		c.1549C>T	p.Pro517Ser	missense	Exon 12 of 12	NP_001012680.1	P08195-5
	SLC3A2	NM_002394.6		c.1546C>T	p.Pro516Ser	missense	Exon 12 of 12	NP_002385.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC3A2	ENST00000338663.12	TSL:1 MANE Select	c.1243C>T	p.Pro415Ser	missense	Exon 9 of 9	ENSP00000340815.7	P08195-2
	SLC3A2	ENST00000377890.6	TSL:1	c.1546C>T	p.Pro516Ser	missense	Exon 12 of 12	ENSP00000367122.2	P08195-1
	SLC3A2	ENST00000377889.6	TSL:1	c.1360C>T	p.Pro454Ser	missense	Exon 10 of 10	ENSP00000367121.2	P08195-3

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 597 AN: 152186 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00103 AC: 258 AN: 250722 AF XY: 0.000738

Gnomad AFR exome AF: 0.0122

Gnomad AMR exome AF: 0.000839

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000454 AC: 664 AN: 1461654 Hom.: 7 Cov.: 31 AF XY: 0.000419 AC XY: 305 AN XY: 727118

African (AFR) AF: 0.0144 AC: 481 AN: 33470

American (AMR) AF: 0.000917 AC: 41 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5766

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1111876

Other (OTH) AF: 0.00118 AC: 71 AN: 60382

GnomAD4 genome AF: 0.00394 AC: 600 AN: 152304 Hom.: 2 Cov.: 32 AF XY: 0.00367 AC XY: 273 AN XY: 74478

African (AFR) AF: 0.0134 AC: 556 AN: 41566

American (AMR) AF: 0.00118 AC: 18 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68024

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00180 Hom.: 5

Bravo AF: 0.00458

ESP6500AA AF: 0.0102 AC: 45

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00119 AC: 145

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0050	T
MetaSVM	Uncertain	0.50	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.18
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.24
Sift	Benign	0.32	T
Sift4G	Benign	0.19	T
Polyphen		0.018	B
Vest4		0.072
MVP		0.69
MPC		0.54
ClinPred		0.0079	T
GERP RS		3.7
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.9
Varity_R		0.14
gMVP		0.22
Mutation Taster		=73/27	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: rs7944051; hg19: chr11-62655818;