chr22-30636469-G-C

Variant names:

• chr22-30636469-G-C
• rs530160904
• NM_001001479.4:c.19G>C

Variant summary

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

The NM_001001479.4(SLC35E4):​c.19G>C​(p.Glu7Gln) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC35E4 NM_001001479.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.524

Genes affected

SLC35E4 (HGNC:17058): (solute carrier family 35 member E4) Predicted to enable antiporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.12470737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35E4	NM_001001479.4	c.19G>C	p.Glu7Gln	missense_variant	Exon 1 of 2	ENST00000343605.5	NP_001001479.1
SLC35E4	NM_001318370.2	c.19G>C	p.Glu7Gln	missense_variant	Exon 1 of 3		NP_001305299.1
SLC35E4	NM_001318371.2	c.19G>C	p.Glu7Gln	missense_variant	Exon 1 of 3		NP_001305300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35E4	ENST00000343605.5	c.19G>C	p.Glu7Gln	missense_variant	Exon 1 of 2	1	NM_001001479.4	ENSP00000339626.4
SLC35E4	ENST00000406566.1	c.19G>C	p.Glu7Gln	missense_variant	Exon 1 of 3	1		ENSP00000384377.1
SLC35E4	ENST00000451479.1	c.-54G>C		upstream_gene_variant		1		ENSP00000413552.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000795 AC: 1 AN: 125734 Hom.: 0 AF XY: 0.0000150 AC XY: 1 AN XY: 66636

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000279

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1349136 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 658306

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19G>C (p.E7Q) alteration is located in exon 1 (coding exon 1) of the SLC35E4 gene. This alteration results from a G to C substitution at nucleotide position 19, causing the glutamic acid (E) at amino acid position 7 to be replaced by a glutamine (Q). 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	0.073
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-0.041
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.027
Sift	Benign	0.071	T;T
Sift4G	Uncertain	0.042	D;T
Polyphen		0.15	B;.
Vest4		0.065
MutPred		0.20		Gain of MoRF binding (P = 0.1049);Gain of MoRF binding (P = 0.1049);
MVP		0.24
MPC		0.55
ClinPred		0.39	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.43

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: rs530160904; hg19: chr22-31032456;