11-57491258-C-T

Variant names:

• chr11-57491258-C-T
• rs114947771
• NM_003627.6:c.1159G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003627.6(SLC43A1):​c.1159G>A​(p.Ala387Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,604,932 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00097 (14 hom.)
• Consequence: SLC43A1 NM_003627.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0400
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025629401).
• BP6: Variant 11-57491258-C-T is Benign according to our data. Variant chr11-57491258-C-T is described in ClinVar as Benign. ClinVar VariationId is 786192.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00537 (818/152324) while in subpopulation AFR AF = 0.0177 (736/41570). AF 95% confidence interval is 0.0166. There are 11 homozygotes in GnomAd4. There are 406 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 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.1159G>A	p.Ala387Thr	missense	Exon 11 of 15	NP_003618.1	O75387-1
	SLC43A1	NM_001198810.2		c.1159G>A	p.Ala387Thr	missense	Exon 11 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.1159G>A	p.Ala387Thr	missense	Exon 11 of 15	ENSP00000278426.3	O75387-1
	SLC43A1	ENST00000528450.5	TSL:1	c.1159G>A	p.Ala387Thr	missense	Exon 11 of 15	ENSP00000435673.1	O75387-1
	SLC43A1	ENST00000901382.1		c.1261G>A	p.Ala421Thr	missense	Exon 12 of 16	ENSP00000571441.1

Frequencies

GnomAD3 genomes AF: 0.00534 AC: 813 AN: 152206 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00217 AC: 530 AN: 244046 AF XY: 0.00205

Gnomad AFR exome AF: 0.0204

Gnomad AMR exome AF: 0.000802

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000345

Gnomad OTH exome AF: 0.00135

GnomAD4 exome AF: 0.000967 AC: 1405 AN: 1452608 Hom.: 14 Cov.: 31 AF XY: 0.000988 AC XY: 713 AN XY: 721690

African (AFR) AF: 0.0197 AC: 655 AN: 33280

American (AMR) AF: 0.000958 AC: 42 AN: 43840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25508

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.00487 AC: 414 AN: 84972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53138

Middle Eastern (MID) AF: 0.00367 AC: 21 AN: 5724

European-Non Finnish (NFE) AF: 0.000142 AC: 157 AN: 1106580

Other (OTH) AF: 0.00193 AC: 116 AN: 60010

GnomAD4 genome AF: 0.00537 AC: 818 AN: 152324 Hom.: 11 Cov.: 32 AF XY: 0.00545 AC XY: 406 AN XY: 74486

African (AFR) AF: 0.0177 AC: 736 AN: 41570

American (AMR) AF: 0.00209 AC: 32 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68022

Other (OTH) AF: 0.00190 AC: 4 AN: 2106

Alfa AF: 0.00254 Hom.: 2

Bravo AF: 0.00606

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0170 AC: 75

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00254 AC: 308

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	0.068
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.40
DANN	Benign	0.93
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.040
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.062
Sift	Benign	0.46	T
Sift4G	Benign	0.33	T
Polyphen		0.0040	B
Vest4		0.056
MVP		0.15
MPC		0.26
ClinPred		0.0036	T
GERP RS		0.014
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.096
Mutation Taster		=100/0	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: rs114947771; hg19: chr11-57258731;