chr1-1665970-C-A

Variant names:

• chr1-1665970-C-A
• rs543333170
• NM_001290264.2:c.1030G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001290264.2(SLC35E2B):​c.1030G>T​(p.Val344Phe) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V344I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC35E2B NM_001290264.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444
• Publications: 1 publications found

Genes affected

SLC35E2B (HGNC:33941): (solute carrier family 35 member E2B) Predicted to enable antiporter activity. Predicted to be involved in transmembrane transport. Predicted to act upstream of or within blastocyst hatching. 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290264.2. 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
	SLC35E2B	NM_001290264.2	MANE Select	c.1030G>T	p.Val344Phe	missense	Exon 10 of 10	NP_001277193.1	P0CK96
	SLC35E2B	NM_001110781.3		c.1030G>T	p.Val344Phe	missense	Exon 9 of 9	NP_001104251.1	P0CK96

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35E2B	ENST00000617444.5	TSL:1 MANE Select	c.1030G>T	p.Val344Phe	missense	Exon 10 of 10	ENSP00000481694.1	P0CK96
	SLC35E2B	ENST00000614300.4	TSL:1	c.732+2357G>T		intron	N/A	ENSP00000478733.1	A0A087WUK8
	SLC35E2B	ENST00000911900.1		c.1195G>T	p.Val399Phe	missense	Exon 9 of 9	ENSP00000581959.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.87	T
PhyloP100		0.44
PrimateAI	Benign	0.37	T
Sift4G	Benign	0.12	T
Polyphen		0.96	D
Vest4		0.68
MutPred		0.75		Loss of MoRF binding (P = 0.0933)
MVP		0.043
ClinPred		0.96	D
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.85
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs543333170; hg19: chr1-1597409; COSMIC: COSV52360175; COSMIC: COSV52360175;