6-118154512-A-G

Position:

• chr6-118154512-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001029858.4(SLC35F1):​c.241A>G​(p.Ser81Gly) variant causes a missense change. 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: 32)
• Consequence: SLC35F1 NM_001029858.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.25

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]

LOC107986523 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.921

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35F1	NM_001029858.4	c.241A>G	p.Ser81Gly	missense_variant	2/8	ENST00000360388.9	NP_001025029.2
LOC107986523	XR_007059722.1	n.188-18534T>C		intron_variant, non_coding_transcript_variant
SLC35F1	NM_001415931.1	c.241A>G	p.Ser81Gly	missense_variant	2/9		NP_001402860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35F1	ENST00000360388.9	c.241A>G	p.Ser81Gly	missense_variant	2/8	1	NM_001029858.4	ENSP00000353557	A2
SLC35F1	ENST00000621341.1	c.64A>G	p.Ser22Gly	missense_variant	1/7	5		ENSP00000484738	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2023

The c.241A>G (p.S81G) alteration is located in exon 2 (coding exon 2) of the SLC35F1 gene. This alteration results from a A to G substitution at nucleotide position 241, causing the serine (S) at amino acid position 81 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Uncertain	-0.089	T
MutationAssessor	Pathogenic	3.1	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.7	D;.
REVEL	Uncertain	0.50
Sift	Uncertain	0.0060	D;.
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.75
MutPred		0.84		Loss of disorder (P = 0.118);.;
MVP		0.37
MPC		1.5
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.54
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-118475675;