1-1665881-G-T

Variant names:

• chr1-1665881-G-T
• rs780556613
• NM_001290264.2:c.1119C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001290264.2(SLC35E2B):​c.1119C>A​(p.His373Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC35E2B NM_001290264.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.586

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04349026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35E2B	NM_001290264.2	c.1119C>A	p.His373Gln	missense_variant	Exon 10 of 10	ENST00000617444.5	NP_001277193.1
SLC35E2B	NM_001110781.3	c.1119C>A	p.His373Gln	missense_variant	Exon 9 of 9		NP_001104251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35E2B	ENST00000617444.5	c.1119C>A	p.His373Gln	missense_variant	Exon 10 of 10	1	NM_001290264.2	ENSP00000481694.1
SLC35E2B	ENST00000614300.4	c.732+2446C>A		intron_variant	Intron 6 of 6	1		ENSP00000478733.1
SLC35E2B	ENST00000611123.1	c.1119C>A	p.His373Gln	missense_variant	Exon 9 of 9	2		ENSP00000484635.1
SLC35E2B	ENST00000480991.1	n.761C>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000650 AC: 1 AN: 153772 Hom.: 0 AF XY: 0.0000122 AC XY: 1 AN XY: 81736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000168

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398812 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689940

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.019	T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.29	T;T
Polyphen		0.0020	B;B
Vest4		0.11
MutPred		0.43		Gain of helix (P = 0.0022);Gain of helix (P = 0.0022);
MVP		0.043
ClinPred		0.17	T
GERP RS		-0.79
Varity_R		0.069
gMVP		0.19

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: rs780556613; hg19: chr1-1597320;