1-1665999-T-C

Variant names:

• chr1-1665999-T-C
• rs1241038402
• NM_001290264.2:c.1001A>G

Variant summary

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

The NM_001290264.2(SLC35E2B):​c.1001A>G​(p.His334Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,398,994 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC35E2B NM_001290264.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35E2B	NM_001290264.2	c.1001A>G	p.His334Arg	missense_variant	Exon 10 of 10	ENST00000617444.5	NP_001277193.1
SLC35E2B	NM_001110781.3	c.1001A>G	p.His334Arg	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.1001A>G	p.His334Arg	missense_variant	Exon 10 of 10	1	NM_001290264.2	ENSP00000481694.1
SLC35E2B	ENST00000614300.4	c.732+2328A>G		intron_variant	Intron 6 of 6	1		ENSP00000478733.1
SLC35E2B	ENST00000611123.1	c.1001A>G	p.His334Arg	missense_variant	Exon 9 of 9	2		ENSP00000484635.1
SLC35E2B	ENST00000480991.1	n.643A>G		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1398994 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689990

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: 9.27e-7

Gnomad4 OTH exome AF: 0.0000345

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1001A>G (p.H334R) alteration is located in exon 9 (coding exon 8) of the SLC35E2B gene. This alteration results from a A to G substitution at nucleotide position 1001, causing the histidine (H) at amino acid position 334 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Benign	18
DANN	Benign	0.80
DEOGEN2	Benign	0.039	T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	.;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.92	T
PrimateAI	Uncertain	0.79	T
Sift4G	Benign	1.0	T;T
Polyphen		0.051	B;B
Vest4		0.82
MutPred		0.71		Gain of MoRF binding (P = 0.0089);Gain of MoRF binding (P = 0.0089);
MVP		0.12
ClinPred		0.95	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs1241038402; hg19: chr1-1597438;