8-11331439-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054028.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35G5	NM_054028.2	MANE Select	c.333C>G	p.Asn111Lys	missense	Exon 1 of 1	NP_473369.1	Q96KT7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35G5	ENST00000382435.5	TSL:6 MANE Select	c.333C>G	p.Asn111Lys	missense	Exon 1 of 1	ENSP00000371872.5	Q96KT7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 154

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.78
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
PromoterAI		-0.021	Neutral
Varity_R		0.18
gMVP		0.46
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr8-11188948;