rs779308316

Variant names:

• chr11-2909588-G-A
• rs779308316
• NM_002555.6:c.414G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002555.6(SLC67A1):​c.414G>A​(p.Met138Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000826 in 1,529,576 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M138V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00084 (2 hom.)
• Consequence: SLC67A1 NM_002555.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39
• Publications: 3 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16769215).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.414G>A	p.Met138Ile	missense	Exon 5 of 11	NP_002546.3
	SLC67A1	NM_001315501.2		c.669G>A	p.Met223Ile	missense	Exon 5 of 11	NP_001302430.1
	SLC67A1	NM_183233.3		c.414G>A	p.Met138Ile	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.414G>A	p.Met138Ile	missense	Exon 5 of 11	ENSP00000497561.1	Q96BI1
	SLC67A1	ENST00000347936.6	TSL:1	c.414G>A	p.Met138Ile	missense	Exon 5 of 11	ENSP00000307859.2	Q96BI1
	SLC67A1	ENST00000380574.5	TSL:1	c.414G>A	p.Met138Ile	missense	Exon 5 of 11	ENSP00000369948.1	Q96BI1

Frequencies

GnomAD3 genomes AF: 0.000677 AC: 103 AN: 152090 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000601 AC: 75 AN: 124746 AF XY: 0.000567

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000291

Gnomad ASJ exome AF: 0.000386

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000159

Gnomad NFE exome AF: 0.00126

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000842 AC: 1160 AN: 1377486 Hom.: 2 Cov.: 35 AF XY: 0.000874 AC XY: 594 AN XY: 679768

African (AFR) AF: 0.0000658 AC: 2 AN: 30418

American (AMR) AF: 0.000198 AC: 7 AN: 35334

Ashkenazi Jewish (ASJ) AF: 0.000161 AC: 4 AN: 24832

East Asian (EAS) AF: 0.00 AC: 0 AN: 35008

South Asian (SAS) AF: 0.0000381 AC: 3 AN: 78712

European-Finnish (FIN) AF: 0.0000571 AC: 2 AN: 35002

Middle Eastern (MID) AF: 0.000432 AC: 2 AN: 4628

European-Non Finnish (NFE) AF: 0.00102 AC: 1097 AN: 1076098

Other (OTH) AF: 0.000748 AC: 43 AN: 57454

GnomAD4 genome AF: 0.000677 AC: 103 AN: 152090 Hom.: 0 Cov.: 33 AF XY: 0.000592 AC XY: 44 AN XY: 74306

African (AFR) AF: 0.0000966 AC: 4 AN: 41416

American (AMR) AF: 0.000458 AC: 7 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00131 AC: 89 AN: 67978

Other (OTH) AF: 0.00144 AC: 3 AN: 2088

Alfa AF: 0.000939 Hom.: 0

Bravo AF: 0.000657

ExAC AF: 0.000235 AC: 17

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

ClinVar submissions as Germline

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	0.92
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.4
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.19
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.054	T
Polyphen		0.98	D
Vest4		0.53
MutPred		0.51		Gain of catalytic residue at L143 (P = 0.0581)
MVP		0.70
MPC		0.59
ClinPred		0.093	T
GERP RS		3.4
Varity_R		0.73
gMVP		0.62
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs779308316; hg19: chr11-2930818;