14-57564178-C-T

Variant names:

• chr14-57564178-C-T
• rs1385919948
• NM_001306087.2:c.1415G>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.1415G>A​(p.Gly472Asp) 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. 14/21 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. G472V) 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: 3.85
• 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=0.21568948).

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.1415G>A	p.Gly472Asp	missense	Exon 8 of 8	NP_001293016.1	G3V4Z9
	SLC35F4	NM_001206920.2		c.1412G>A	p.Gly471Asp	missense	Exon 8 of 8	NP_001193849.1
	SLC35F4	NM_001352015.3		c.1406G>A	p.Gly469Asp	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.1415G>A	p.Gly472Asp	missense	Exon 8 of 8	ENSP00000452086.1	G3V4Z9
	SLC35F4	ENST00000554729.5	TSL:1	c.1046G>A	p.Gly349Asp	missense	Exon 8 of 8	ENSP00000451990.1	A4IF30-2
	SLC35F4	ENST00000557254.5	TSL:1	n.*776G>A		non_coding_transcript_exon	Exon 10 of 10	ENSP00000450836.1	G3V2S4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 248106 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.040
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.8
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.042
Sift	Benign	0.074	T
Sift4G	Benign	0.43	T
Polyphen		0.036	B
Vest4		0.10
MutPred		0.35		Gain of catalytic residue at G508 (P = 2e-04)
MVP		0.48
MPC		0.052
ClinPred		0.74	D
GERP RS		4.3
Varity_R		0.16
gMVP		0.45
Mutation Taster		=75/25	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: rs1385919948; hg19: chr14-58030896;