Genetic Variant SLC35G1:p.Ala143Pro (chr10-93900819-G-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001134658.3(SLC35G1):c.427G>C(p.Ala143Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. A143T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC35G1
NM_001134658.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.15

Publications

0 publications found

Variant links:

Genes affected

SLC35G1 (HGNC:26607): (solute carrier family 35 member G1) This gene encodes a transmembrane protein which is a member of the drug/metabolite transporter protein superfamily. The encoded protein may play a role in the regulation of calcium levels inside the cell. [provided by RefSeq, Sep 2016]

SLC35G1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.973

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134658.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC35G1	NM_001134658.3	MANE Select	c.427G>C	p.Ala143Pro	missense	Exon 3 of 3	NP_001128130.1	Q2M3R5-1
SLC35G1	NM_153226.4		c.424G>C	p.Ala142Pro	missense	Exon 3 of 3	NP_694958.1	Q2M3R5-2
SLC35G1	NM_001345993.2		c.376G>C	p.Ala126Pro	missense	Exon 3 of 3	NP_001332922.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC35G1	ENST00000427197.2	TSL:1 MANE Select	c.427G>C	p.Ala143Pro	missense	Exon 3 of 3	ENSP00000400932.1	Q2M3R5-1
SLC35G1	ENST00000483386.5	TSL:1	n.128-5433G>C		intron	N/A	ENSP00000473766.1	S4R2Y7
SLC35G1	ENST00000603665.1	TSL:1	n.179-5433G>C		intron	N/A	ENSP00000473862.1	D3DR41

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111882

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.042

MetaRNN

Pathogenic

0.97

MetaSVM

Uncertain

-0.092

MutationAssessor

Pathogenic

3.0

PhyloP100

4.2

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.48

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.012

Polyphen

0.97

Vest4

0.80

MutPred

0.84

Loss of catalytic residue at A143 (P = 0.0402)

MVP

0.48

MPC

0.82

ClinPred

0.98

GERP RS

3.1

Varity_R

0.75

gMVP

0.95

Mutation Taster

=44/56

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over