rs138542621

Variant names:

• chr1-168231880-C-G
• NM_199344.3:c.197C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-168231880-C-G
• chr1-168231880-C-T

Variant summary

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

The NM_199344.3(SFT2D2):​c.197C>G​(p.Ala66Gly) 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. 12/21 in silico tools predict a benign 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. A66V) 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: 1.47

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, 0.879

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFT2D2	NM_199344.3	c.197C>G	p.Ala66Gly	missense_variant	Exon 3 of 8	ENST00000271375.7	NP_955376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFT2D2	ENST00000271375.7	c.197C>G	p.Ala66Gly	missense_variant	Exon 3 of 8	1	NM_199344.3	ENSP00000271375.3
SFT2D2	ENST00000367829.5	c.197C>G	p.Ala66Gly	missense_variant	Exon 3 of 6	5		ENSP00000356803.1
SFT2D2	ENST00000630869.1	c.197C>G	p.Ala66Gly	missense_variant	Exon 3 of 7	4		ENSP00000486492.1
SFT2D2	ENST00000471981.1	n.450C>G		non_coding_transcript_exon_variant	Exon 4 of 7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;T
Eigen	Benign	-0.049
Eigen_PC	Benign	-0.0018
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.88	.;D;D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	.;.;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.1	D;.;D
REVEL	Benign	0.27
Sift	Benign	0.037	D;.;T
Sift4G	Uncertain	0.054	T;T;D
Polyphen		0.11	.;.;B
Vest4		0.78
MutPred		0.77		Loss of catalytic residue at A66 (P = 0.0199);Loss of catalytic residue at A66 (P = 0.0199);Loss of catalytic residue at A66 (P = 0.0199);
MVP		0.60
MPC		0.34
ClinPred		0.69	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-168201118;