rs543432257

Variant names:

• chr11-2909599-A-G
• rs543432257
• NM_002555.6:c.425A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-2909599-A-G
• chr11-2909599-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002555.6(SLC67A1):​c.425A>G​(p.Asp142Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000523 in 1,530,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: SLC67A1 NM_002555.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57
• Publications: 1 publications found

Genes affected

SLC67A1 (HGNC:10964): (solute carrier family 22 member 18) This gene is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene is imprinted, with preferential expression from the maternal allele. Mutations in this gene have been found in Wilms' tumor and lung cancer. This protein may act as a transporter of organic cations, and have a role in the transport of chloroquine and quinidine-related compounds in kidney. Several alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21832287).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002555.6. 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
	SLC67A1	NM_002555.6	MANE Select	c.425A>G	p.Asp142Gly	missense	Exon 5 of 11	NP_002546.3
	SLC67A1	NM_001315501.2		c.680A>G	p.Asp227Gly	missense	Exon 5 of 11	NP_001302430.1
	SLC67A1	NM_183233.3		c.425A>G	p.Asp142Gly	missense	Exon 5 of 11	NP_899056.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC67A1	ENST00000649076.2	MANE Select	c.425A>G	p.Asp142Gly	missense	Exon 5 of 11	ENSP00000497561.1	Q96BI1
	SLC67A1	ENST00000347936.6	TSL:1	c.425A>G	p.Asp142Gly	missense	Exon 5 of 11	ENSP00000307859.2	Q96BI1
	SLC67A1	ENST00000380574.5	TSL:1	c.425A>G	p.Asp142Gly	missense	Exon 5 of 11	ENSP00000369948.1	Q96BI1

Frequencies

GnomAD3 genomes AF: 0.0000922 AC: 14 AN: 151764 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000727

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00194

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: 0.000104 AC: 13 AN: 125272 AF XY: 0.0000869

Gnomad AFR exome AF: 0.000395

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00114

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000479 AC: 66 AN: 1378472 Hom.: 0 Cov.: 35 AF XY: 0.0000426 AC XY: 29 AN XY: 680352

African (AFR) AF: 0.0000328 AC: 1 AN: 30454

American (AMR) AF: 0.00 AC: 0 AN: 35394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24848

East Asian (EAS) AF: 0.000400 AC: 14 AN: 34996

South Asian (SAS) AF: 0.00 AC: 0 AN: 78730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4776

European-Non Finnish (NFE) AF: 0.0000353 AC: 38 AN: 1076322

Other (OTH) AF: 0.000226 AC: 13 AN: 57512

GnomAD4 genome AF: 0.0000922 AC: 14 AN: 151876 Hom.: 0 Cov.: 33 AF XY: 0.0000808 AC XY: 6 AN XY: 74278

African (AFR) AF: 0.0000725 AC: 3 AN: 41382

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00195 AC: 10 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67894

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.0000869 Hom.: 0

Bravo AF: 0.000125

ExAC AF: 0.0000260 AC: 2

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	Pathogenic	0.83
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.32	N
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.6
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.87		Gain of catalytic residue at S144 (P = 0.052)
MVP		0.80
MPC		0.80
ClinPred		0.31	T
GERP RS		2.9
Varity_R		0.72
gMVP		0.71
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs543432257; hg19: chr11-2930829;