Genetic Variant SLC60A1:p.Arg6His (chr1-205569086-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_181644.5(SLC60A1):c.17G>A(p.Arg6His) variant causes a missense change. The variant allele was found at a frequency of 0.00001 in 1,493,820 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 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

SLC60A1
NM_181644.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.50

Publications

1 publications found

Variant links:

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]

SLC60A1 links:

MFSD4A-AS1 (HGNC:):

MFSD4A-AS1 links:

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

SLC60A1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.10414705).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC60A1	NM_181644.5	MANE Select	c.17G>A	p.Arg6His	missense	Exon 1 of 10	NP_857595.3
SLC60A1-AS1	NR_027086.2		n.177+43C>T		intron	N/A
SLC60A1-AS1	NR_152721.1		n.177+43C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MFSD4A	ENST00000367147.9	TSL:1 MANE Select	c.17G>A	p.Arg6His	missense	Exon 1 of 10	ENSP00000356115.4	Q8N468-1
MFSD4A	ENST00000873628.1		c.17G>A	p.Arg6His	missense	Exon 1 of 10	ENSP00000543687.1
MFSD4A	ENST00000873627.1		c.17G>A	p.Arg6His	missense	Exon 1 of 10	ENSP00000543686.1

Frequencies

GnomAD3 genomes

AF:

0.0000529

AC:

AN:

151348

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000363

AC:

AN:

110074

AF XY:

0.0000335

show subpopulations

Gnomad AFR exome

AF:

0.000624

Gnomad AMR exome

AF:

0.000103

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:

0.00000447

AC:

AN:

1342364

Hom.:

Cov.:

AF XY:

0.00000454

AC XY:

AN XY:

661084

show subpopulations

African (AFR)

AF:

0.000147

AC:

AN:

27288

American (AMR)

AF:

0.0000328

AC:

AN:

30518

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23620

East Asian (EAS)

AF:

0.00

AC:

AN:

29552

South Asian (SAS)

AF:

0.00

AC:

AN:

74558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4988

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1051136

Other (OTH)

AF:

0.0000181

AC:

AN:

55278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000594

AC:

AN:

151456

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74004

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41484

American (AMR)

AF:

0.00

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67728

Other (OTH)

AF:

0.00

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000150

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0047

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.64

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

PhyloP100

5.5

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.4

REVEL

Benign

0.10

Sift

Benign

0.058

Sift4G

Benign

0.096

Polyphen

0.40

Vest4

0.077

MutPred

0.54

Loss of methylation at R6 (P = 0.0141)

MVP

0.38

MPC

0.69

ClinPred

0.071

GERP RS

1.7

PromoterAI

-0.19

Neutral

(source)

Varity_R

0.13

gMVP

0.62

Mutation Taster

=67/33

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over