1-155137616-G-A

Variant names:

• chr1-155137616-G-A
• rs758437827
• NM_018845.4:c.338G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018845.4(SLC50A1):​c.338G>A​(p.Gly113Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,058 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC50A1 NM_018845.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39541203).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018845.4. 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.338G>A	p.Gly113Asp	missense	Exon 4 of 6	NP_061333.2	Q9BRV3-1
	SLC50A1	NM_001287587.2		c.317G>A	p.Gly106Asp	missense	Exon 4 of 6	NP_001274516.1
	SLC50A1	NM_001287591.2		c.224G>A	p.Gly75Asp	missense	Exon 4 of 6	NP_001274520.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC50A1	ENST00000368404.9	TSL:1 MANE Select	c.338G>A	p.Gly113Asp	missense	Exon 4 of 6	ENSP00000357389.4	Q9BRV3-1
	SLC50A1	ENST00000368401.6	TSL:1	c.173G>A	p.Gly58Asp	missense	Exon 3 of 5	ENSP00000357386.5	Q9BRV3-2
	SLC50A1	ENST00000303343.12	TSL:1	c.283-363G>A		intron	N/A	ENSP00000306146.8	Q9BRV3-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251490 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 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: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

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

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.00000824 AC: 1

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	0.75
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.6
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.23
Sift	Benign	0.21	T
Sift4G	Benign	0.094	T
Polyphen		0.88	P
Vest4		0.76
MutPred		0.48		Gain of catalytic residue at G113 (P = 0.1716)
MVP		0.13
MPC		0.70
ClinPred		0.65	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.66
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs758437827; hg19: chr1-155110092;