3-136855514-C-A

Variant names:

• chr3-136855514-C-A
• rs1458462848
• NM_025246.3:c.1054C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_025246.3(SLC35G2):​c.1054C>A​(p.His352Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.51

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35G2	NM_025246.3	c.1054C>A	p.His352Asn	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.1054C>A	p.His352Asn	missense_variant	Exon 2 of 2	1	NM_025246.3	ENSP00000400839.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1054C>A (p.H352N) alteration is located in exon 2 (coding exon 1) of the SLC35G2 gene. This alteration results from a C to A substitution at nucleotide position 1054, causing the histidine (H) at amino acid position 352 to be replaced by an asparagine (N). 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	0.47
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.47	N;N
REVEL	Benign	0.24
Sift	Benign	0.26	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.99	D;D
Vest4		0.90
MutPred		0.51		Loss of glycosylation at S348 (P = 0.026);Loss of glycosylation at S348 (P = 0.026);
MVP		0.70
MPC		0.52
ClinPred		0.74	D
GERP RS		5.9
Varity_R		0.081
gMVP		0.88

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: rs1458462848; hg19: chr3-136574356;