Genetic Variant SLC35F6:p.Leu13Leu (chr2-26764388-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4BP6_ModerateBP7BS2

The NM_017877.4(SLC35F6):c.39C>T(p.Leu13Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,551,110 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 6 hom. )

Consequence

SLC35F6
NM_017877.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.302

Variant links:

Genes affected

SLC35F6 (HGNC:26055): (solute carrier family 35 member F6) Predicted to enable transmembrane transporter activity. Involved in negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway and positive regulation of cell population proliferation. Located in several cellular components, including lysosomal membrane; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SLC35F6 links:

CENPA (HGNC:1851): (centromere protein A) Centromeres are the differentiated chromosomal domains that specify the mitotic behavior of chromosomes. This gene encodes a centromere protein which contains a histone H3 related histone fold domain that is required for targeting to the centromere. Centromere protein A is proposed to be a component of a modified nucleosome or nucleosome-like structure in which it replaces 1 or both copies of conventional histone H3 in the (H3-H4)2 tetrameric core of the nucleosome particle. The protein is a replication-independent histone that is a member of the histone H3 family. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2015]

CENPA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.13).

BP6

Variant 2-26764388-C-T is Benign according to our data. Variant chr2-26764388-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650751.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.302 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35F6	NM_017877.4 link	c.39C>T	p.Leu13Leu	synonymous_variant	Exon 1 of 6	ENST00000344420.10	NP_060347.2	Q8N357

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35F6	ENST00000344420.10 link	c.39C>T	p.Leu13Leu	synonymous_variant	Exon 1 of 6	1	NM_017877.4	ENSP00000345528.5		Q8N357

Frequencies

GnomAD3 genomes

AF:

0.00248

AC:

378

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00428

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00203

AC:

316

AN:

156002

Hom.:

AF XY:

0.00203

AC XY:

167

AN XY:

82232

show subpopulations

Gnomad AFR exome

AF:

0.000115

Gnomad AMR exome

AF:

0.000485

Gnomad ASJ exome

AF:

0.000117

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00110

Gnomad FIN exome

AF:

0.00241

Gnomad NFE exome

AF:

0.00382

Gnomad OTH exome

AF:

0.00227

GnomAD4 exome

AF:

0.00261

AC:

3655

AN:

1398740

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

1854

AN XY:

689908

show subpopulations

Gnomad4 AFR exome

AF:

0.000317

Gnomad4 AMR exome

AF:

0.000784

Gnomad4 ASJ exome

AF:

0.000238

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00109

Gnomad4 FIN exome

AF:

0.00283

Gnomad4 NFE exome

AF:

0.00304

Gnomad4 OTH exome

AF:

0.00186

GnomAD4 genome

AF:

0.00248

AC:

378

AN:

152370

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

179

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.00428

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00387

Hom.:

Bravo

AF:

0.00255

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC35F6: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

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