10-93900819-G-C

Variant names:

• chr10-93900819-G-C
• rs144043787
• NM_001134658.3:c.427G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.15
• Publications: 0 publications found

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]

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35G1	NM_001134658.3	c.427G>C	p.Ala143Pro	missense_variant	Exon 3 of 3	ENST00000427197.2	NP_001128130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35G1	ENST00000427197.2	c.427G>C	p.Ala143Pro	missense_variant	Exon 3 of 3	1	NM_001134658.3	ENSP00000400932.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461700 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727150

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111882

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	-0.092	T
MutationAssessor	Pathogenic	3.0	M;.
PhyloP100		4.2
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.97	D;D
Vest4		0.80
MutPred		0.84		Loss of catalytic residue at A143 (P = 0.0402);.;
MVP		0.48
MPC		0.82
ClinPred		0.98	D
GERP RS		3.1
Varity_R		0.75
gMVP		0.95
Mutation Taster		=44/56	disease causing

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: rs144043787; hg19: chr10-95660576;