14-57564353-C-T

Variant names:

• chr14-57564353-C-T
• rs558357715
• NM_001306087.2:c.1240G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001306087.2(SLC35F4):​c.1240G>A​(p.Val414Met) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V414L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC35F4 NM_001306087.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.08
• 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]

LOC105370519 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15230158).

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.1240G>A	p.Val414Met	missense	Exon 8 of 8	NP_001293016.1	G3V4Z9
	SLC35F4	NM_001206920.2		c.1237G>A	p.Val413Met	missense	Exon 8 of 8	NP_001193849.1
	SLC35F4	NM_001352015.3		c.1231G>A	p.Val411Met	missense	Exon 8 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.1240G>A	p.Val414Met	missense	Exon 8 of 8	ENSP00000452086.1	G3V4Z9
	SLC35F4	ENST00000554729.5	TSL:1	c.871G>A	p.Val291Met	missense	Exon 8 of 8	ENSP00000451990.1	A4IF30-2
	SLC35F4	ENST00000557254.5	TSL:1	n.*601G>A		non_coding_transcript_exon	Exon 10 of 10	ENSP00000450836.1	G3V2S4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	0.018
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.081
Sift	Benign	0.071	T
Sift4G	Benign	0.12	T
Polyphen		0.13	B
Vest4		0.15
MutPred		0.41		Gain of catalytic residue at K447 (P = 0.0718)
MVP		0.33
MPC		0.087
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.13
gMVP		0.63
Mutation Taster		=80/20	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: rs558357715; hg19: chr14-58031071;