chr1-205569086-G-T

Variant names:

• chr1-205569086-G-T
• rs747518493
• NM_181644.5:c.17G>T

Variant summary

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

The NM_181644.5(SLC60A1):​c.17G>T​(p.Arg6Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000745 in 1,342,364 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: SLC60A1 NM_181644.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.50
• Publications: 1 publications found

Genes affected

SLC60A1 (HGNC:25433): (major facilitator superfamily domain containing 4A) Predicted to enable glucose transmembrane transporter activity. Predicted to be involved in glucose transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD4A-AS1 (HGNC:):

SLC60A1-AS1 (HGNC:27632): (MFSD4A antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181644.5. 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
	SLC60A1	NM_181644.5	MANE Select	c.17G>T	p.Arg6Leu	missense	Exon 1 of 10	NP_857595.3
	SLC60A1-AS1	NR_027086.2		n.177+43C>A		intron	N/A
	SLC60A1-AS1	NR_152721.1		n.177+43C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD4A	ENST00000367147.9	TSL:1 MANE Select	c.17G>T	p.Arg6Leu	missense	Exon 1 of 10	ENSP00000356115.4	Q8N468-1
	MFSD4A	ENST00000873628.1		c.17G>T	p.Arg6Leu	missense	Exon 1 of 10	ENSP00000543687.1
	MFSD4A	ENST00000873627.1		c.17G>T	p.Arg6Leu	missense	Exon 1 of 10	ENSP00000543686.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.45e-7 AC: 1 AN: 1342364 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 661084

African (AFR) AF: 0.0000366 AC: 1 AN: 27288

American (AMR) AF: 0.00 AC: 0 AN: 30518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23620

East Asian (EAS) AF: 0.00 AC: 0 AN: 29552

South Asian (SAS) AF: 0.00 AC: 0 AN: 74558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4988

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1051136

Other (OTH) AF: 0.00 AC: 0 AN: 55278

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-1.0	T
PhyloP100		5.5
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.98	D
Vest4		0.38
MutPred		0.57		Loss of methylation at R6 (P = 0.0141)
MVP		0.62
MPC		1.4
ClinPred		0.97	D
GERP RS		1.7
PromoterAI		0.11	Neutral
Varity_R		0.31
gMVP		0.75
Mutation Taster		=64/36	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: rs747518493; hg19: chr1-205538214;