ENST00000368401.6:c.40C>G

Variant names:

• chr1-155136299-C-G
• rs751851099
• ENST00000368401.6:c.40C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000368401.6(SLC50A1):​c.40C>G​(p.Leu14Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000436 in 1,605,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SLC50A1 ENST00000368401.6 missense, splice_region
• Scores: Splicing: ADA: 0.009369
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.38
• Publications: 1 publications found

Genes affected

SLC50A1 (HGNC:30657): (solute carrier family 50 member 1) Enables glucoside transmembrane transporter activity. Predicted to be involved in carbohydrate transport. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15448725).
• BP6: Variant 1-155136299-C-G is Benign according to our data. Variant chr1-155136299-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3444804.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368401.6. 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
	SLC50A1	NM_018845.4	MANE Select	c.81C>G	p.Leu27Leu	splice_region synonymous	Exon 2 of 6	NP_061333.2	Q9BRV3-1
	SLC50A1	NM_001287587.2		c.40C>G	p.Leu14Val	missense splice_region	Exon 2 of 6	NP_001274516.1
	SLC50A1	NM_001287591.2		c.-16C>G		splice_region	Exon 2 of 6	NP_001274520.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC50A1	ENST00000368401.6	TSL:1	c.40C>G	p.Leu14Val	missense splice_region	Exon 2 of 5	ENSP00000357386.5	Q9BRV3-2
	SLC50A1	ENST00000368404.9	TSL:1 MANE Select	c.81C>G	p.Leu27Leu	splice_region synonymous	Exon 2 of 6	ENSP00000357389.4	Q9BRV3-1
	SLC50A1	ENST00000303343.12	TSL:1	c.81C>G	p.Leu27Leu	splice_region synonymous	Exon 2 of 5	ENSP00000306146.8	Q9BRV3-3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152080 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1453636 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722500

African (AFR) AF: 0.00 AC: 0 AN: 33288

American (AMR) AF: 0.00 AC: 0 AN: 43666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25916

East Asian (EAS) AF: 0.00 AC: 0 AN: 39340

South Asian (SAS) AF: 0.00 AC: 0 AN: 84878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1107826

Other (OTH) AF: 0.00 AC: 0 AN: 60100

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152080 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74272

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

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	Benign	0.070
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	16
DANN	Benign	0.78
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.4
PROVEAN	Benign	0.30	N
REVEL	Benign	0.078
Sift	Pathogenic	0.0	D
Polyphen		0.0090	B
Vest4		0.15
MutPred		0.11		Gain of sheet (P = 0.0827)
MVP		0.13
ClinPred		0.98	D
GERP RS		4.4
PromoterAI		0.0058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=41/59	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0094
dbscSNV1_RF	Benign	0.12
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: rs751851099; hg19: chr1-155108775;