8-11331439-C-G

Variant names:

• chr8-11331439-C-G
• NM_054028.2:c.333C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_054028.2(SLC35G5):​c.333C>G​(p.Asn111Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC35G5 NM_054028.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.783

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35G5	NM_054028.2	c.333C>G	p.Asn111Lys	missense_variant	Exon 1 of 1	ENST00000382435.5	NP_473369.1
MTMR9	XM_047422125.1	c.1487-5245C>G		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.333C>G	p.Asn111Lys	missense_variant	Exon 1 of 1	6	NM_054028.2	ENSP00000371872.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 154

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.333C>G (p.N111K) alteration is located in exon 1 (coding exon 1) of the SLC35G5 gene. This alteration results from a C to G substitution at nucleotide position 333, causing the asparagine (N) at amino acid position 111 to be replaced by a lysine (K). 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	Uncertain	0.36
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.056	N
M_CAP	Benign	0.0022	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.17
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.016	D
Polyphen		0.97	D
Vest4		0.29
MutPred		0.73		Gain of ubiquitination at N111 (P = 0.023);
MVP		0.18
MPC		0.36
ClinPred		0.98	D
GERP RS		-0.68
Varity_R		0.18
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-11188948;