rs747437793

Variant names:

• chr1-168236731-C-G
• rs747437793
• NM_199344.3:c.374C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-168236731-C-G
• chr1-168236731-C-T

Variant summary

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

The NM_199344.3(SFT2D2):​c.374C>G​(p.Ala125Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A125V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SFT2D2 NM_199344.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.18

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.776

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFT2D2	NM_199344.3	c.374C>G	p.Ala125Gly	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.374C>G	p.Ala125Gly	missense_variant	Exon 6 of 8	1	NM_199344.3	ENSP00000271375.3
SFT2D2	ENST00000367829.5	c.292C>G	p.His98Asp	missense_variant	Exon 5 of 6	5		ENSP00000356803.1
SFT2D2	ENST00000630869.1	c.292C>G	p.His98Asp	missense_variant	Exon 5 of 7	4		ENSP00000486492.1
SFT2D2	ENST00000471981.1	n.627C>G		non_coding_transcript_exon_variant	Exon 7 of 7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251442 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135896

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461870 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0070	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.61	P
Vest4		0.53
MutPred		0.71		Gain of catalytic residue at L126 (P = 0.078);
MVP		0.52
MPC		0.57
ClinPred		0.95	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.38
gMVP		0.85

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: rs747437793; hg19: chr1-168205969;