8-11331257-G-C

Variant names:

• chr8-11331257-G-C
• rs778498438
• NM_054028.2:c.151G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_054028.2(SLC35G5):​c.151G>C​(p.Ala51Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,613,796 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: SLC35G5 NM_054028.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.586

Genes affected

SLC35G5 (HGNC:15546): (solute carrier family 35 member G5) This gene is intronless and probably arose from retrotransposition of a similar gene. It has high sequence similarity to the gene encoding acyl-malonyl condensing enzyme on chromosome 17. [provided by RefSeq, Aug 2011]

MTMR9 (HGNC:14596): (myotubularin related protein 9) This gene encodes a myotubularin-related protein that is atypical to most other members of the myotubularin-related protein family because it has no dual-specificity phosphatase domain. The encoded protein contains a double-helical motif similar to the SET interaction domain, which is thought to have a role in the control of cell proliferation. In mouse, a protein similar to the encoded protein binds with MTMR7, and together they dephosphorylate phosphatidylinositol 3-phosphate and inositol 1,3-bisphosphate. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28667966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35G5	NM_054028.2	c.151G>C	p.Ala51Pro	missense_variant	Exon 1 of 1	ENST00000382435.5	NP_473369.1
MTMR9	XM_047422125.1	c.1487-5427G>C		intron_variant	Intron 9 of 10		XP_047278081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35G5	ENST00000382435.5	c.151G>C	p.Ala51Pro	missense_variant	Exon 1 of 1	6	NM_054028.2	ENSP00000371872.5

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.000103

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251324 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135834

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000130 AC: 190 AN: 1461598 Hom.: 1 Cov.: 157 AF XY: 0.000140 AC XY: 102 AN XY: 727088

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000166

Gnomad4 OTH exome AF: 0.0000663

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74342

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.151G>C (p.A51P) alteration is located in exon 1 (coding exon 1) of the SLC35G5 gene. This alteration results from a G to C substitution at nucleotide position 151, causing the alanine (A) at amino acid position 51 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.0078	N
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.17
Sift	Benign	0.19	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.63		Gain of catalytic residue at P50 (P = 0.018);
MVP		0.24
MPC		0.45
ClinPred		0.24	T
GERP RS		0.34
Varity_R		0.37
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs778498438; hg19: chr8-11188766;