chr22-30636469-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001001479.4(SLC35E4):​c.19G>T​(p.Glu7*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,349,134 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (1 hom.)
• Consequence: SLC35E4 NM_001001479.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001479.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35E4	NM_001001479.4	MANE Select	c.19G>T	p.Glu7*	stop_gained	Exon 1 of 2	NP_001001479.1	Q6ICL7-1
	SLC35E4	NM_001318370.2		c.19G>T	p.Glu7*	stop_gained	Exon 1 of 3	NP_001305299.1	Q6ICL7-2
	SLC35E4	NM_001318371.2		c.19G>T	p.Glu7*	stop_gained	Exon 1 of 3	NP_001305300.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35E4	ENST00000343605.5	TSL:1 MANE Select	c.19G>T	p.Glu7*	stop_gained	Exon 1 of 2	ENSP00000339626.4	Q6ICL7-1
	SLC35E4	ENST00000406566.1	TSL:1	c.19G>T	p.Glu7*	stop_gained	Exon 1 of 3	ENSP00000384377.1	Q6ICL7-2
	SLC35E4	ENST00000451479.1	TSL:1	c.-54G>T		upstream_gene	N/A	ENSP00000413552.1	H7C3S2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1349134 Hom.: 1 Cov.: 30 AF XY: 0.00000304 AC XY: 2 AN XY: 658306

African (AFR) AF: 0.00 AC: 0 AN: 30462

American (AMR) AF: 0.00 AC: 0 AN: 31020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22490

East Asian (EAS) AF: 0.00 AC: 0 AN: 35052

South Asian (SAS) AF: 0.0000270 AC: 2 AN: 74150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4394

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1050106

Other (OTH) AF: 0.00 AC: 0 AN: 55574

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.49
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Benign	0.70	D
PhyloP100		0.52
Vest4		0.026
GERP RS		4.5
PromoterAI		-0.086	Neutral
Mutation Taster		=32/168	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs530160904; hg19: chr22-31032456;