1-1666019-G-C

Variant names:

• chr1-1666019-G-C
• NM_001290264.2:c.981C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001290264.2(SLC35E2B):​c.981C>G​(p.Ser327Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,397,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S327S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SLC35E2B NM_001290264.2 missense, splice_region
• Scores: Splicing: ADA: 0.000002147
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35E2B	NM_001290264.2	c.981C>G	p.Ser327Arg	missense_variant, splice_region_variant	Exon 10 of 10	ENST00000617444.5	NP_001277193.1
SLC35E2B	NM_001110781.3	c.981C>G	p.Ser327Arg	missense_variant, splice_region_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.981C>G	p.Ser327Arg	missense_variant, splice_region_variant	Exon 10 of 10	1	NM_001290264.2	ENSP00000481694.1
SLC35E2B	ENST00000614300.4	c.732+2308C>G		intron_variant	Intron 6 of 6	1		ENSP00000478733.1
SLC35E2B	ENST00000611123.1	c.981C>G	p.Ser327Arg	missense_variant, splice_region_variant	Exon 9 of 9	2		ENSP00000484635.1
SLC35E2B	ENST00000480991.1	n.623C>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1397196 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 688728

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: 0.0000126

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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Benign	0.69
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.85	.;T
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Uncertain	0.34	D
PrimateAI	Uncertain	0.74	T
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	D;D
Vest4		0.98
MutPred		0.93		Gain of MoRF binding (P = 0.0267);Gain of MoRF binding (P = 0.0267);
MVP		0.66
ClinPred		0.96	D
GERP RS		-9.8
Varity_R		0.91
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000021
dbscSNV1_RF	Benign	0.074
SpliceAI score (max)		0.010		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: chr1-1597458;