1-234320125-T-C

Position:

• chr1-234320125-T-C

Variant summary

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

The NM_173508.4(SLC35F3):​c.1175T>C​(p.Ile392Thr) variant causes a missense change involving the alteration of a conserved nucleotide. 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: SLC35F3 NM_173508.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.46

Genes affected

SLC35F3 (HGNC:23616): (solute carrier family 35 member F3) Involved in thiamine transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.873

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35F3	NM_173508.4	c.1175T>C	p.Ile392Thr	missense_variant	7/8	ENST00000366618.8	NP_775779.1
SLC35F3	NM_001300845.2	c.968T>C	p.Ile323Thr	missense_variant	6/7		NP_001287774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35F3	ENST00000366618.8	c.1175T>C	p.Ile392Thr	missense_variant	7/8	2	NM_173508.4	ENSP00000355577
SLC35F3	ENST00000366617.3	c.968T>C	p.Ile323Thr	missense_variant	6/7	1		ENSP00000355576	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Apr 26, 2024

The c.1175T>C (p.I392T) alteration is located in exon 7 (coding exon 7) of the SLC35F3 gene. This alteration results from a T to C substitution at nucleotide position 1175, causing the isoleucine (I) at amino acid position 392 to be replaced by a threonine (T). 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	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	.;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Uncertain	-0.094	T
MutationAssessor	Uncertain	2.1	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.021	D;T
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;D
Vest4		0.87
MutPred		0.72		.;Loss of stability (P = 0.0351);
MVP		0.33
MPC		1.7
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.27
gMVP		0.84

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: chr1-234455871;