11-57491720-C-G

Variant names:

• chr11-57491720-C-G
• rs35730224
• NM_003627.6:c.1014G>C

Variant summary

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

The NM_003627.6(SLC43A1):​c.1014G>C​(p.Glu338Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,614,262 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (7 hom.)
• Consequence: SLC43A1 NM_003627.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.267
• Publications: 2 publications found

Genes affected

SLC43A1 (HGNC:9225): (solute carrier family 43 member 1) SLC43A1 belongs to the system L family of plasma membrane carrier proteins that transports large neutral amino acids (Babu et al., 2003 [PubMed 12930836]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003510207).
• BP6: Variant 11-57491720-C-G is Benign according to our data. Variant chr11-57491720-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 728328.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_003627.6. 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
	SLC43A1	NM_003627.6	MANE Select	c.1014G>C	p.Glu338Asp	missense	Exon 9 of 15	NP_003618.1	O75387-1
	SLC43A1	NM_001198810.2		c.1014G>C	p.Glu338Asp	missense	Exon 9 of 15	NP_001185739.1	O75387-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC43A1	ENST00000278426.8	TSL:1 MANE Select	c.1014G>C	p.Glu338Asp	missense	Exon 9 of 15	ENSP00000278426.3	O75387-1
	SLC43A1	ENST00000528450.5	TSL:1	c.1014G>C	p.Glu338Asp	missense	Exon 9 of 15	ENSP00000435673.1	O75387-1
	SLC43A1	ENST00000901382.1		c.1116G>C	p.Glu372Asp	missense	Exon 10 of 16	ENSP00000571441.1

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 284 AN: 152260 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00659

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00253

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00214 AC: 538 AN: 251442 AF XY: 0.00224

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00809

Gnomad NFE exome AF: 0.00255

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00207 AC: 3033 AN: 1461884 Hom.: 7 Cov.: 32 AF XY: 0.00205 AC XY: 1494 AN XY: 727242

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.00121 AC: 54 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00103 AC: 89 AN: 86258

European-Finnish (FIN) AF: 0.00685 AC: 366 AN: 53414

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.00216 AC: 2406 AN: 1112008

Other (OTH) AF: 0.00171 AC: 103 AN: 60396

GnomAD4 genome AF: 0.00186 AC: 284 AN: 152378 Hom.: 3 Cov.: 32 AF XY: 0.00195 AC XY: 145 AN XY: 74514

African (AFR) AF: 0.000385 AC: 16 AN: 41596

American (AMR) AF: 0.000980 AC: 15 AN: 15310

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.00659 AC: 70 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00253 AC: 172 AN: 68032

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00191 Hom.: 0

Bravo AF: 0.00172

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00279 AC: 24

ExAC AF: 0.00190 AC: 231

EpiCase AF: 0.00289

EpiControl AF: 0.00332

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	Benign	0.093
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.8
DANN	Benign	0.97
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.41	N
PhyloP100		-0.27
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.045
Sift	Benign	0.35	T
Sift4G	Benign	0.69	T
Polyphen		0.0030	B
Vest4		0.080
MutPred		0.22		Loss of helix (P = 0.0196)
MVP		0.29
MPC		0.25
ClinPred		0.0048	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.071
gMVP		0.18
Mutation Taster		=99/1	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: rs35730224; hg19: chr11-57259193;