chr6-117907732-C-G

Variant names:

• chr6-117907732-C-G
• rs756765575
• NM_001029858.4:c.6C>G

Variant summary

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

The NM_001029858.4(SLC35F1):​c.6C>G​(p.Ile2Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 1,523,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SLC35F1 NM_001029858.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.325
• Publications: 0 publications found

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]

SLC35F1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

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=0.15949723).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029858.4. 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
	SLC35F1	NM_001029858.4	MANE Select	c.6C>G	p.Ile2Met	missense	Exon 1 of 8	NP_001025029.2	Q5T1Q4-1
	SLC35F1	NM_001415931.1		c.6C>G	p.Ile2Met	missense	Exon 1 of 9	NP_001402860.1	Q5T1Q4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35F1	ENST00000360388.9	TSL:1 MANE Select	c.6C>G	p.Ile2Met	missense	Exon 1 of 8	ENSP00000353557.4	Q5T1Q4-1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151740 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000583 AC: 1 AN: 171490 AF XY: 0.0000102

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: 0.0000127

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1371602 Hom.: 0 Cov.: 27 AF XY: 0.00000293 AC XY: 2 AN XY: 683712

African (AFR) AF: 0.00 AC: 0 AN: 28400

American (AMR) AF: 0.00 AC: 0 AN: 37682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24294

East Asian (EAS) AF: 0.0000310 AC: 1 AN: 32208

South Asian (SAS) AF: 0.00 AC: 0 AN: 80858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5176

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1069188

Other (OTH) AF: 0.00 AC: 0 AN: 56864

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151740 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74120

African (AFR) AF: 0.00 AC: 0 AN: 41344

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67870

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.00000876 AC: 1

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	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.5
DANN	Benign	0.64
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.33	T
M_CAP	Pathogenic	0.58	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.33
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.19	N
REVEL	Benign	0.068
Sift	Pathogenic	0.0	D
Polyphen		0.044	B
Vest4		0.30
MutPred		0.19		Loss of catalytic residue at I2 (P = 0.02)
MVP		0.061
MPC		0.60
ClinPred		0.069	T
GERP RS		1.5
PromoterAI		-0.083	Neutral
Varity_R		0.18
gMVP		0.37
Mutation Taster		=89/11	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: rs756765575; hg19: chr6-118228895;