6-118277507-C-T

Position:

• chr6-118277507-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001029858.4(SLC35F1):​c.808C>T​(p.His270Tyr) 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. 14/20 in silico tools predict a benign outcome for this variant. 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: 3.46

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21969548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35F1	NM_001029858.4	c.808C>T	p.His270Tyr	missense_variant	6/8	ENST00000360388.9	NP_001025029.2
SLC35F1	NM_001415931.1	c.808C>T	p.His270Tyr	missense_variant	6/9		NP_001402860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35F1	ENST00000360388.9	c.808C>T	p.His270Tyr	missense_variant	6/8	1	NM_001029858.4	ENSP00000353557.4
SLC35F1	ENST00000621341.1	c.631C>T	p.His211Tyr	missense_variant	5/7	5		ENSP00000484738.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jun 16, 2024

The c.808C>T (p.H270Y) alteration is located in exon 6 (coding exon 6) of the SLC35F1 gene. This alteration results from a C to T substitution at nucleotide position 808, causing the histidine (H) at amino acid position 270 to be replaced by a tyrosine (Y). 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	0.21
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Benign	0.69
DEOGEN2	Benign	0.067	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	0.015
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.2	N;.
REVEL	Benign	0.10
Sift	Benign	0.63	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.048	B;.
Vest4		0.35
MutPred		0.58		Gain of catalytic residue at L265 (P = 0.0668);.;
MVP		0.13
MPC		0.74
ClinPred		0.89	D
GERP RS		5.0
Varity_R		0.27
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-118598670;