22-30646676-C-A

Position:

• chr22-30646676-C-A

Variant summary

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

The NM_001001479.4(SLC35E4):​c.698C>A​(p.Ala233Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC35E4 NM_001001479.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.66

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35E4	NM_001001479.4	c.698C>A	p.Ala233Glu	missense_variant	2/2	ENST00000343605.5
SLC35E4	NM_001318370.2	c.620-2484C>A		intron_variant
SLC35E4	NM_001318371.2	c.619+9607C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35E4	ENST00000343605.5	c.698C>A	p.Ala233Glu	missense_variant	2/2	1	NM_001001479.4	P1
SLC35E4	ENST00000406566.1	c.620-2484C>A		intron_variant		1
SLC35E4	ENST00000451479.1	c.547+9607C>A		intron_variant		1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2023

The c.698C>A (p.A233E) alteration is located in exon 2 (coding exon 2) of the SLC35E4 gene. This alteration results from a C to A substitution at nucleotide position 698, causing the alanine (A) at amino acid position 233 to be replaced by a glutamic acid (E). 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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	0.90	D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.51
Sift	Benign	0.12	T
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.52
MutPred		0.62		Gain of relative solvent accessibility (P = 0.09);
MVP		0.83
MPC		1.1
ClinPred		0.87	D
GERP RS		3.8
Varity_R		0.15
gMVP		0.70

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: rs141444677; hg19: chr22-31042663;