NM_001306087.2:c.620T>G

Variant names:

• chr14-57581401-A-C
• NM_001306087.2:c.620T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001306087.2(SLC35F4):​c.620T>G​(p.Leu207Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC35F4 NM_001306087.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.25
• Publications: 0 publications found

Genes affected

SLC35F4 (HGNC:19845): (solute carrier family 35 member F4) 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]

SLC35F4-AS1 (HGNC:58292):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.855

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001306087.2. 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
	SLC35F4	NM_001306087.2	MANE Select	c.620T>G	p.Leu207Arg	missense	Exon 4 of 8	NP_001293016.1	G3V4Z9
	SLC35F4	NM_001206920.2		c.617T>G	p.Leu206Arg	missense	Exon 4 of 8	NP_001193849.1
	SLC35F4	NM_001352015.3		c.611T>G	p.Leu204Arg	missense	Exon 4 of 8	NP_001338944.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35F4	ENST00000556826.6	TSL:5 MANE Select	c.620T>G	p.Leu207Arg	missense	Exon 4 of 8	ENSP00000452086.1	G3V4Z9
	SLC35F4	ENST00000554729.5	TSL:1	c.251T>G	p.Leu84Arg	missense	Exon 4 of 8	ENSP00000451990.1	A4IF30-2
	SLC35F4	ENST00000557254.5	TSL:1	n.251T>G		non_coding_transcript_exon	Exon 4 of 10	ENSP00000450836.1	G3V2S4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.90
PhyloP100		9.3
Varity_R		0.78
gMVP		0.74
Mutation Taster		=42/58	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-58048119;