chr2-26764388-C-T

Variant names:

• chr2-26764388-C-T
• rs142072865
• NM_017877.4:c.39C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4 BP6_Moderate BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.302
• Publications: 2 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017877.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35F6	NM_017877.4	MANE Select	c.39C>T	p.Leu13Leu	synonymous	Exon 1 of 6	NP_060347.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35F6	ENST00000344420.10	TSL:1 MANE Select	c.39C>T	p.Leu13Leu	synonymous	Exon 1 of 6	ENSP00000345528.5	Q8N357
	SLC35F6	ENST00000414029.1	TSL:1	n.39C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000396256.1	F8WCT7
	SLC35F6	ENST00000429494.5	TSL:1	n.39C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000397623.1	F8WB19

Frequencies

GnomAD3 genomes AF: 0.00248 AC: 378 AN: 152250 Hom.: 1 Cov.: 33

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

GnomAD2 exomes AF: 0.00203 AC: 316 AN: 156002 AF XY: 0.00203

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 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.: 6 Cov.: 31 AF XY: 0.00269 AC XY: 1854 AN XY: 689908

African (AFR) AF: 0.000317 AC: 10 AN: 31588

American (AMR) AF: 0.000784 AC: 28 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.000238 AC: 6 AN: 25170

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35728

South Asian (SAS) AF: 0.00109 AC: 86 AN: 79234

European-Finnish (FIN) AF: 0.00283 AC: 138 AN: 48798

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5698

European-Non Finnish (NFE) AF: 0.00304 AC: 3275 AN: 1078834

Other (OTH) AF: 0.00186 AC: 108 AN: 57992

GnomAD4 genome AF: 0.00248 AC: 378 AN: 152370 Hom.: 1 Cov.: 33 AF XY: 0.00240 AC XY: 179 AN XY: 74498

African (AFR) AF: 0.000433 AC: 18 AN: 41594

American (AMR) AF: 0.00209 AC: 32 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00292 AC: 31 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00428 AC: 291 AN: 68036

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00387 Hom.: 0

Bravo AF: 0.00255

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.13
CADD	Benign	19
DANN	Benign	0.94
PhyloP100		0.30
PromoterAI		0.0035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=298/2	polymorphism

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

Other links and lift over

dbSNP: rs142072865; hg19: chr2-26987256;