rs1314751007

Variant names:

• chr1-168239144-T-A
• rs1314751007
• NM_199344.3:c.427T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-168239144-T-A
• chr1-168239144-T-C
• chr1-168239144-T-G

Variant summary

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

The NM_199344.3(SFT2D2):​c.427T>A​(p.Phe143Ile) 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 (★). 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.25

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

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, 0.923

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFT2D2	NM_199344.3	c.427T>A	p.Phe143Ile	missense_variant	Exon 7 of 8	ENST00000271375.7	NP_955376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFT2D2	ENST00000271375.7	c.427T>A	p.Phe143Ile	missense_variant	Exon 7 of 8	1	NM_199344.3	ENSP00000271375.3
SFT2D2	ENST00000367829.5	c.*18T>A		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000356803.1
SFT2D2	ENST00000630869.1	c.*18T>A		3_prime_UTR_variant	Exon 6 of 7	4		ENSP00000486492.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 10, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.427T>A (p.F143I) alteration is located in exon 7 (coding exon 7) of the SFT2D2 gene. This alteration results from a T to A substitution at nucleotide position 427, causing the phenylalanine (F) at amino acid position 143 to be replaced by an isoleucine (I). 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	0.93
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.25	B
Vest4		0.75
MutPred		0.88		Gain of catalytic residue at P145 (P = 0.0327);
MVP		0.29
MPC		0.67
ClinPred		0.98	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.49
gMVP		0.94

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

LitVar

Other links and lift over

dbSNP: rs1314751007; hg19: chr1-168208382;