1-1668376-T-C

Variant names:

• chr1-1668376-T-C
• NM_001290264.2:c.931A>G

Variant summary

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

The NM_001290264.2(SLC35E2B):​c.931A>G​(p.Ser311Gly) 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: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC35E2B NM_001290264.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54
• Publications: 0 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, 0.748

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.931A>G	p.Ser311Gly	missense	Exon 9 of 10	NP_001277193.1	P0CK96
	SLC35E2B	NM_001110781.3		c.931A>G	p.Ser311Gly	missense	Exon 8 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.931A>G	p.Ser311Gly	missense	Exon 9 of 10	ENSP00000481694.1	P0CK96
	SLC35E2B	ENST00000614300.4	TSL:1	c.683A>G	p.Glu228Gly	missense	Exon 6 of 7	ENSP00000478733.1	A0A087WUK8
	SLC35E2B	ENST00000911900.1		c.1096A>G	p.Ser366Gly	missense	Exon 8 of 9	ENSP00000581959.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1460806 Hom.: 0 Cov.: 91 AF XY: 0.00000138 AC XY: 1 AN XY: 726632

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33342

American (AMR) AF: 0.00 AC: 0 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111700

Other (OTH) AF: 0.00 AC: 0 AN: 60352

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.40	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Pathogenic	0.75	D
PhyloP100		7.5
Sift4G	Uncertain	0.012	D
Vest4		0.55
MVP		0.37
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.51
Mutation Taster		=30/70	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr1-1599815;