1-168235174-A-G

Variant names:

• chr1-168235174-A-G
• rs1164542557
• NM_199344.3:c.310A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_199344.3(SFT2D2):​c.310A>G​(p.Met104Val) 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 benign outcome for this variant. 15/21 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. M104L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFT2D2 NM_199344.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036136687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFT2D2	NM_199344.3	c.310A>G	p.Met104Val	missense_variant	Exon 4 of 8	ENST00000271375.7	NP_955376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFT2D2	ENST00000271375.7	c.310A>G	p.Met104Val	missense_variant	Exon 4 of 8	1	NM_199344.3	ENSP00000271375.3
SFT2D2	ENST00000367829.5	c.237-1415A>G		intron_variant	Intron 3 of 5	5		ENSP00000356803.1
SFT2D2	ENST00000630869.1	c.237-1415A>G		intron_variant	Intron 3 of 6	4		ENSP00000486492.1
SFT2D2	ENST00000471981.1	n.563A>G		non_coding_transcript_exon_variant	Exon 5 of 7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251488 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135918

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 Cov.: 30

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.052
DANN	Benign	0.68
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.2	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.68	N
REVEL	Benign	0.042
Sift	Benign	0.79	T
Sift4G	Benign	0.89	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.59		Gain of catalytic residue at M104 (P = 0.0244);
MVP		0.095
MPC		0.30
ClinPred		0.036	T
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.64

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

LitVar

Other links and lift over

dbSNP: rs1164542557; hg19: chr1-168204412;