rs1438009763

Variant names:

• chr1-168231554-A-T
• rs1438009763
• NM_199344.3:c.104A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_199344.3(SFT2D2):​c.104A>T​(p.Lys35Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar 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: 6.39

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFT2D2	NM_199344.3	c.104A>T	p.Lys35Ile	missense_variant	Exon 2 of 8	ENST00000271375.7	NP_955376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFT2D2	ENST00000271375.7	c.104A>T	p.Lys35Ile	missense_variant	Exon 2 of 8	1	NM_199344.3	ENSP00000271375.3
SFT2D2	ENST00000367829.5	c.104A>T	p.Lys35Ile	missense_variant	Exon 2 of 6	5		ENSP00000356803.1
SFT2D2	ENST00000630869.1	c.104A>T	p.Lys35Ile	missense_variant	Exon 2 of 7	4		ENSP00000486492.1
SFT2D2	ENST00000471981.1	n.357A>T		non_coding_transcript_exon_variant	Exon 3 of 7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 21, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.104A>T (p.K35I) alteration is located in exon 2 (coding exon 2) of the SFT2D2 gene. This alteration results from a A to T substitution at nucleotide position 104, causing the lysine (K) at amino acid position 35 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	0.59
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	.;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	.;.;M
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-7.9	D;.;D
REVEL	Benign	0.26
Sift	Uncertain	0.019	D;.;D
Sift4G	Pathogenic	0.0010	D;D;T
Polyphen		0.94	.;.;P
Vest4		0.74
MutPred		0.57		Loss of methylation at K35 (P = 0.0132);Loss of methylation at K35 (P = 0.0132);Loss of methylation at K35 (P = 0.0132);
MVP		0.47
MPC		0.56
ClinPred		0.99	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.75
gMVP		0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs1438009763; hg19: chr1-168200792;