NM_199344.3:c.368G>A

Variant names:

• chr1-168236725-G-A
• rs1280997023
• NM_199344.3:c.368G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_199344.3(SFT2D2):​c.368G>A​(p.Gly123Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SFT2D2 NM_199344.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.111812115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFT2D2	NM_199344.3	c.368G>A	p.Gly123Glu	missense_variant	Exon 6 of 8	ENST00000271375.7	NP_955376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFT2D2	ENST00000271375.7	c.368G>A	p.Gly123Glu	missense_variant	Exon 6 of 8	1	NM_199344.3	ENSP00000271375.3
SFT2D2	ENST00000367829.5	c.286G>A	p.Asp96Asn	missense_variant	Exon 5 of 6	5		ENSP00000356803.1
SFT2D2	ENST00000630869.1	c.286G>A	p.Asp96Asn	missense_variant	Exon 5 of 7	4		ENSP00000486492.1
SFT2D2	ENST00000471981.1	n.621G>A		non_coding_transcript_exon_variant	Exon 7 of 7	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.368G>A (p.G123E) alteration is located in exon 6 (coding exon 6) of the SFT2D2 gene. This alteration results from a G to A substitution at nucleotide position 368, causing the glycine (G) at amino acid position 123 to be replaced by a glutamic acid (E). 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	0.67
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0050	T;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.47	.;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.86	T
PROVEAN	Benign	0.29	N;.
REVEL	Benign	0.17
Sift	Benign	0.67	T;.
Sift4G	Benign	0.27	T;T
Vest4		0.25
MutPred		0.41		Loss of glycosylation at S101 (P = 0.2558);Loss of glycosylation at S101 (P = 0.2558);
MVP		0.31
ClinPred		0.99	D
GERP RS		5.2

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: rs1280997023; hg19: chr1-168205963;