rs372038494

Variant names:

• chr2-26776457-C-G
• rs372038494
• NM_017877.4:c.621C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-26776457-C-G
• chr2-26776457-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017877.4(SLC35F6):​c.621C>G​(p.His207Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SLC35F6 NM_017877.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.621C>G	p.His207Gln	missense	Exon 5 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.621C>G	p.His207Gln	missense	Exon 5 of 6	ENSP00000345528.5	Q8N357
	SLC35F6	ENST00000414029.1	TSL:1	n.*293C>G		non_coding_transcript_exon	Exon 4 of 5	ENSP00000396256.1	F8WCT7
	SLC35F6	ENST00000429494.5	TSL:1	n.*380C>G		non_coding_transcript_exon	Exon 4 of 5	ENSP00000397623.1	F8WB19

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	20
DANN	Benign	0.83
DEOGEN2	Benign	0.032	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.8
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.12
Sift	Benign	0.082	T
Sift4G	Benign	0.23	T
Polyphen		0.16	B
Vest4		0.91
MutPred		0.46		Loss of methylation at R210 (P = 0.0421)
MVP		0.68
MPC		0.78
ClinPred		0.87	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.82
Mutation Taster		=63/37	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: rs372038494; hg19: chr2-26999325;