1-1669687-C-G

Variant names:

• chr1-1669687-C-G
• rs527702193
• NM_001290264.2:c.811G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001290264.2(SLC35E2B):​c.811G>C​(p.Val271Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,379,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign 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. V271F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SLC35E2B NM_001290264.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.857
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09550542).

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.811G>C	p.Val271Leu	missense	Exon 8 of 10	NP_001277193.1	P0CK96
	SLC35E2B	NM_001110781.3		c.811G>C	p.Val271Leu	missense	Exon 7 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.811G>C	p.Val271Leu	missense	Exon 8 of 10	ENSP00000481694.1	P0CK96
	SLC35E2B	ENST00000614300.4	TSL:1	c.587-1215G>C		intron	N/A	ENSP00000478733.1	A0A087WUK8
	SLC35E2B	ENST00000911900.1		c.976G>C	p.Val326Leu	missense	Exon 7 of 9	ENSP00000581959.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1379010 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 675630

⚠️ 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: 31202

American (AMR) AF: 0.00 AC: 0 AN: 35332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25022

East Asian (EAS) AF: 0.00 AC: 0 AN: 35194

South Asian (SAS) AF: 0.00 AC: 0 AN: 78770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4056

European-Non Finnish (NFE) AF: 9.40e-7 AC: 1 AN: 1063840

Other (OTH) AF: 0.00 AC: 0 AN: 56822

⚠️ 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.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.33
DANN	Benign	0.28
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.52	N
PhyloP100		0.86
PrimateAI	Benign	0.31	T
Sift4G	Benign	0.37	T
Polyphen		0.0050	B
Vest4		0.15
MutPred		0.56		Gain of helix (P = 0.132)
MVP		0.043
ClinPred		0.039	T
GERP RS		-1.5
Varity_R		0.023
gMVP		0.34
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs527702193; hg19: chr1-1601126;