3-136854624-A-G

Variant names:

• chr3-136854624-A-G
• rs1937878670
• NM_025246.3:c.164A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025246.3(SLC35G2):​c.164A>G​(p.Lys55Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC35G2 NM_025246.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00

Genes affected

SLC35G2 (HGNC:28480): (solute carrier family 35 member G2) Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

NCK1-DT (HGNC:49645): (NCK1 divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07492027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35G2	NM_025246.3	c.164A>G	p.Lys55Arg	missense_variant	Exon 2 of 2	ENST00000446465.3	NP_079522.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35G2	ENST00000446465.3	c.164A>G	p.Lys55Arg	missense_variant	Exon 2 of 2	1	NM_025246.3	ENSP00000400839.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 21, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.164A>G (p.K55R) alteration is located in exon 2 (coding exon 1) of the SLC35G2 gene. This alteration results from a A to G substitution at nucleotide position 164, causing the lysine (K) at amino acid position 55 to be replaced by an arginine (R). 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	0.070
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T;T
Eigen	Benign	-0.083
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	.;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.17	N;N
REVEL	Benign	0.11
Sift	Benign	0.41	T;T
Sift4G	Benign	0.87	T;T
Polyphen		0.0010	B;B
Vest4		0.069
MutPred		0.20		Gain of glycosylation at S59 (P = 0.0131);Gain of glycosylation at S59 (P = 0.0131);
MVP		0.25
MPC		0.096
ClinPred		0.81	D
GERP RS		5.5
Varity_R		0.099
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs1937878670; hg19: chr3-136573466;