10-101034851-T-C

Variant names:

• chr10-101034851-T-C
• NM_030971.6:c.157T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030971.6(SFXN3):​c.157T>C​(p.Tyr53His) 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: SFXN3 NM_030971.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.25

Genes affected

SFXN3 (HGNC:16087): (sideroflexin 3) Enables serine transmembrane transporter activity. Involved in serine import into mitochondrion. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFXN3	NM_030971.6	c.157T>C	p.Tyr53His	missense_variant	Exon 3 of 12	ENST00000393459.6	NP_112233.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFXN3	ENST00000393459.6	c.157T>C	p.Tyr53His	missense_variant	Exon 3 of 12	5	NM_030971.6	ENSP00000377103.1
SFXN3	ENST00000698791.1	c.157T>C	p.Tyr53His	missense_variant	Exon 2 of 11			ENSP00000513933.1
SFXN3	ENST00000698792.1	c.157T>C	p.Tyr53His	missense_variant	Exon 2 of 10			ENSP00000513934.1
SFXN3	ENST00000489434.3	n.157T>C		non_coding_transcript_exon_variant	Exon 1 of 6	3		ENSP00000474564.1

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

Mar 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.169T>C (p.Y57H) alteration is located in exon 3 (coding exon 2) of the SFXN3 gene. This alteration results from a T to C substitution at nucleotide position 169, causing the tyrosine (Y) at amino acid position 57 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	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.53	T
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.032	D;D
Vest4		0.68
MutPred		0.76		.;Gain of disorder (P = 0.0393);
MVP		0.43
MPC		0.51
ClinPred		0.99	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
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: chr10-102794608;