1-168239146-C-A

Variant names:

• chr1-168239146-C-A
• NM_199344.3:c.429C>A
• SFT2D2 p.Phe143Leu

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_199344.3(SFT2D2):​c.429C>A​(p.Phe143Leu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F143V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFT2D2 NM_199344.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• Publications: 0 publications found

Genes affected

SFT2D2 (HGNC:25140): (SFT2 domain containing 2) Predicted to be involved in protein transport and vesicle-mediated transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.839

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199344.3. 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
	SFT2D2	NM_199344.3	MANE Select	c.429C>A	p.Phe143Leu	missense	Exon 7 of 8	NP_955376.1	O95562

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFT2D2	ENST00000271375.7	TSL:1 MANE Select	c.429C>A	p.Phe143Leu	missense	Exon 7 of 8	ENSP00000271375.3	O95562
	SFT2D2	ENST00000873660.1		c.393C>A	p.Phe131Leu	missense	Exon 6 of 7	ENSP00000543719.1
	SFT2D2	ENST00000873663.1		c.261C>A	p.Phe87Leu	missense	Exon 5 of 6	ENSP00000543722.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.011
Eigen_PC	Benign	0.077
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.10
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Varity_R		0.43
gMVP		0.90
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-168208384;