6-118235536-G-C

Position:

• chr6-118235536-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001029858.4(SLC35F1):​c.377G>C​(p.Arg126Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC35F1 NM_001029858.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61

Genes affected

SLC35F1 (HGNC:21483): (solute carrier family 35 member F1) 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35F1	NM_001029858.4	c.377G>C	p.Arg126Pro	missense_variant	3/8	ENST00000360388.9	NP_001025029.2
SLC35F1	NM_001415931.1	c.377G>C	p.Arg126Pro	missense_variant	3/9		NP_001402860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35F1	ENST00000360388.9	c.377G>C	p.Arg126Pro	missense_variant	3/8	1	NM_001029858.4	ENSP00000353557	A2
SLC35F1	ENST00000621341.1	c.200G>C	p.Arg67Pro	missense_variant	2/7	5		ENSP00000484738	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2023

The c.377G>C (p.R126P) alteration is located in exon 3 (coding exon 3) of the SLC35F1 gene. This alteration results from a G to C substitution at nucleotide position 377, causing the arginine (R) at amino acid position 126 to be replaced by a proline (P). 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	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	0.97	D
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.5	D;.
REVEL	Uncertain	0.47
Sift	Uncertain	0.0030	D;.
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.95	P;.
Vest4		0.54
MutPred		0.62		Loss of MoRF binding (P = 0.0052);.;
MVP		0.75
MPC		1.7
ClinPred		0.97	D
GERP RS		4.9
Varity_R		0.77
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-118556699;