1-1665884-T-G

Variant names:

• chr1-1665884-T-G
• NM_001290264.2:c.1116A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001290264.2(SLC35E2B):​c.1116A>C​(p.Gln372His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 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: 7.1e-7 (0 hom.)
• Consequence: SLC35E2B NM_001290264.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22035193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35E2B	NM_001290264.2	c.1116A>C	p.Gln372His	missense_variant	Exon 10 of 10	ENST00000617444.5	NP_001277193.1
SLC35E2B	NM_001110781.3	c.1116A>C	p.Gln372His	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.1116A>C	p.Gln372His	missense_variant	Exon 10 of 10	1	NM_001290264.2	ENSP00000481694.1
SLC35E2B	ENST00000614300.4	c.732+2443A>C		intron_variant	Intron 6 of 6	1		ENSP00000478733.1
SLC35E2B	ENST00000611123.1	c.1116A>C	p.Gln372His	missense_variant	Exon 9 of 9	2		ENSP00000484635.1
SLC35E2B	ENST00000480991.1	n.758A>C		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398840 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689954

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000280

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: 0.00

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	0.19
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.093
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	.;D
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.46	T
Sift4G	Uncertain	0.034	D;D
Polyphen		0.73	P;P
Vest4		0.44
MutPred		0.59		Loss of methylation at K369 (P = 0.0888);Loss of methylation at K369 (P = 0.0888);
MVP		0.068
ClinPred		0.99	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1597323;