3-136854689-C-T

Variant names:

• chr3-136854689-C-T
• rs1576923258
• NM_025246.3:c.229C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025246.3(SLC35G2):​c.229C>T​(p.Pro77Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 2.31

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04886383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35G2	NM_025246.3	c.229C>T	p.Pro77Ser	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.229C>T	p.Pro77Ser	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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.229C>T (p.P77S) alteration is located in exon 2 (coding exon 1) of the SLC35G2 gene. This alteration results from a C to T substitution at nucleotide position 229, causing the proline (P) at amino acid position 77 to be replaced by a serine (S). 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	0.063
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.5
DANN	Benign	0.73
DEOGEN2	Benign	0.0092	T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.46	.;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.44	N;N
REVEL	Benign	0.026
Sift	Benign	0.29	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.0	B;B
Vest4		0.065
MutPred		0.20		Loss of catalytic residue at P77 (P = 0.0081);Loss of catalytic residue at P77 (P = 0.0081);
MVP		0.16
MPC		0.12
ClinPred		0.031	T
GERP RS		3.5
Varity_R		0.017
gMVP		0.40

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: rs1576923258; hg19: chr3-136573531;