Variant 11-107804722-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017515.5(SLC35F2):c.780A>T(p.Lys260Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,451,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC35F2
NM_017515.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

Variant links:

Genes affected

SLC35F2 (HGNC:23615): (solute carrier family 35 member F2) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC35F2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33771464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35F2	NM_017515.5 linkuse as main transcript	c.780A>T	p.Lys260Asn	missense_variant	6/8	ENST00000525815.6	NP_059985.2	Q8IXU6-1
SLC35F2	XM_047427146.1 linkuse as main transcript	c.639A>T	p.Lys213Asn	missense_variant	6/8		XP_047283102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35F2	ENST00000525815.6 linkuse as main transcript	c.780A>T	p.Lys260Asn	missense_variant	6/8	1	NM_017515.5	ENSP00000436785.1		Q8IXU6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000820

AC:

AN:

243854

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1451642

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722280

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000770

Gnomad4 EAS exome

AF:

0.0000253

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.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 03, 2022

The c.780A>T (p.K260N) alteration is located in exon 6 (coding exon 6) of the SLC35F2 gene. This alteration results from a A to T substitution at nucleotide position 780, causing the lysine (K) at amino acid position 260 to be replaced by an asparagine (N). 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

Benign

0.29

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

T;.;.

Eigen

Benign

0.082

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.040

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

2.0

M;M;.

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.096

Sift

Benign

0.071

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.15

B;.;.

Vest4

0.57

MutPred

0.47

Loss of ubiquitination at K260 (P = 0.0192);Loss of ubiquitination at K260 (P = 0.0192);.;

MVP

0.69

MPC

0.26

ClinPred

0.45

GERP RS

5.4

Varity_R

0.30

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over