NM_018845.4:c.283C>T

Variant names:

• chr1-155137561-C-T
• rs375567260
• NM_018845.4:c.283C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018845.4(SLC50A1):​c.283C>T​(p.Arg95Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: SLC50A1 NM_018845.4 missense, splice_region
• Scores: Splicing: ADA: 0.3919
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.926
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16381696).

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.283C>T	p.Arg95Cys	missense splice_region	Exon 4 of 6	NP_061333.2	Q9BRV3-1
	SLC50A1	NM_001287587.2		c.262C>T	p.Arg88Cys	missense splice_region	Exon 4 of 6	NP_001274516.1
	SLC50A1	NM_001287586.2		c.145C>T	p.Arg49Cys	missense splice_region	Exon 3 of 5	NP_001274515.1	A0A087WXX5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC50A1	ENST00000368404.9	TSL:1 MANE Select	c.283C>T	p.Arg95Cys	missense splice_region	Exon 4 of 6	ENSP00000357389.4	Q9BRV3-1
	SLC50A1	ENST00000368401.6	TSL:1	c.118C>T	p.Arg40Cys	missense splice_region	Exon 3 of 5	ENSP00000357386.5	Q9BRV3-2
	SLC50A1	ENST00000303343.12	TSL:1	c.283-418C>T		intron	N/A	ENSP00000306146.8	Q9BRV3-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251032 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000281 AC: 41 AN: 1461660 Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19 AN XY: 727146

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

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

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

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

European-Non Finnish (NFE) AF: 0.0000351 AC: 39 AN: 1111890

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

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	Benign	0.25
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.082	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.93
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.33
MVP		0.18
MPC		0.65
ClinPred		0.34	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.35
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.39
dbscSNV1_RF	Benign	0.44
SpliceAI score (max)		0.060		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: rs375567260; hg19: chr1-155110037;