6-118267030-G-C

Position:

• chr6-118267030-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001029858.4(SLC35F1):​c.513G>C​(p.Leu171Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC35F1 NM_001029858.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.240

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4138074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35F1	NM_001029858.4	c.513G>C	p.Leu171Phe	missense_variant	4/8	ENST00000360388.9	NP_001025029.2
SLC35F1	NM_001415931.1	c.513G>C	p.Leu171Phe	missense_variant	4/9		NP_001402860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35F1	ENST00000360388.9	c.513G>C	p.Leu171Phe	missense_variant	4/8	1	NM_001029858.4	ENSP00000353557.4
SLC35F1	ENST00000621341.1	c.336G>C	p.Leu112Phe	missense_variant	3/7	5		ENSP00000484738.1

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

Nov 13, 2024

The c.513G>C (p.L171F) alteration is located in exon 4 (coding exon 4) of the SLC35F1 gene. This alteration results from a G to C substitution at nucleotide position 513, causing the leucine (L) at amino acid position 171 to be replaced by a phenylalanine (F). 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	0.12
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T;.
Eigen	Benign	-0.087
Eigen_PC	Benign	0.0041
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.5	N;.
REVEL	Uncertain	0.35
Sift	Benign	0.21	T;.
Sift4G	Benign	0.22	T;T
Polyphen		0.38	B;.
Vest4		0.47
MutPred		0.53		Loss of helix (P = 0.2271);.;
MVP		0.71
MPC		1.4
ClinPred		0.86	D
GERP RS		3.1
Varity_R		0.10
gMVP		0.68

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: chr6-118588193;