chr1-234323030-G-C

Position:

• chr1-234323030-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173508.4(SLC35F3):​c.1260G>C​(p.Gln420His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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: 0.315

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06578237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35F3	NM_173508.4	c.1260G>C	p.Gln420His	missense_variant	8/8	ENST00000366618.8	NP_775779.1
SLC35F3	NM_001300845.2	c.1053G>C	p.Gln351His	missense_variant	7/7		NP_001287774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35F3	ENST00000366618.8	c.1260G>C	p.Gln420His	missense_variant	8/8	2	NM_173508.4	ENSP00000355577
SLC35F3	ENST00000366617.3	c.1053G>C	p.Gln351His	missense_variant	7/7	1		ENSP00000355576	P1

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

Jan 31, 2024

The c.1260G>C (p.Q420H) alteration is located in exon 8 (coding exon 8) of the SLC35F3 gene. This alteration results from a G to C substitution at nucleotide position 1260, causing the glutamine (Q) at amino acid position 420 to be replaced by a histidine (H). 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	0.087
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.42	.;N
MutationTaster	Benign	0.95	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.61	N;N
REVEL	Benign	0.028
Sift	Benign	0.14	T;T
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.013	B;B
Vest4		0.099
MutPred		0.40		.;Gain of sheet (P = 0.1208);
MVP		0.18
MPC		0.70
ClinPred		0.12	T
GERP RS		-0.068
Varity_R		0.047
gMVP		0.53

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: chr1-234458776;