Genetic Variant NM_001029858.4:c.44C>T (chr6-117907770-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001029858.4(SLC35F1):c.44C>T(p.Ser15Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,559,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.000011 ( 0 hom. )

Consequence

SLC35F1
NM_001029858.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.730

Publications

0 publications found

Variant links:

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

SLC35F1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042826712).

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.44C>T	p.Ser15Leu	missense	Exon 1 of 8	NP_001025029.2	Q5T1Q4-1
	SLC35F1	NM_001415931.1		c.44C>T	p.Ser15Leu	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.44C>T	p.Ser15Leu	missense	Exon 1 of 8	ENSP00000353557.4	Q5T1Q4-1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151576

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000114

AC:

AN:

1408126

Hom.:

Cov.:

AF XY:

0.0000157

AC XY:

AN XY:

700654

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29602

American (AMR)

AF:

0.00

AC:

AN:

41202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24828

East Asian (EAS)

AF:

0.00

AC:

AN:

34528

South Asian (SAS)

AF:

0.00

AC:

AN:

83120

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5186

European-Non Finnish (NFE)

AF:

0.0000146

AC:

AN:

1094584

Other (OTH)

AF:

0.00

AC:

AN:

58450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151576

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74040

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41300

American (AMR)

AF:

0.00

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67812

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0092

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.46

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.34

PhyloP100

0.73

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.25

REVEL

Benign

0.044

Sift

Benign

0.22

Sift4G

Benign

0.094

Polyphen

0.0

Vest4

0.10

MutPred

0.21

Loss of glycosylation at S15 (P = 0.0032)

MVP

0.076

MPC

0.52

ClinPred

0.42

GERP RS

1.5

Varity_R

0.086

gMVP

0.47

Mutation Taster

=94/6

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over