6-166329561-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_145169.3(SFT2D1):​c.179G>T​(p.Gly60Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,456,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SFT2D1
NM_145169.3 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88
Variant links:
Genes affected
SFT2D1 (HGNC:21102): (SFT2 domain containing 1) Predicted to be involved in protein transport and vesicle-mediated transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.861

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SFT2D1NM_145169.3 linkc.179G>T p.Gly60Val missense_variant Exon 3 of 8 ENST00000361731.4 NP_660152.1 Q8WV19
SFT2D1NR_130112.2 linkn.266G>T non_coding_transcript_exon_variant Exon 4 of 9
SFT2D1NR_130113.2 linkn.266G>T non_coding_transcript_exon_variant Exon 4 of 7
SFT2D1NR_130114.2 linkn.257G>T non_coding_transcript_exon_variant Exon 4 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SFT2D1ENST00000361731.4 linkc.179G>T p.Gly60Val missense_variant Exon 3 of 8 1 NM_145169.3 ENSP00000354590.3 Q8WV19
SFT2D1ENST00000487841.5 linkn.268G>T non_coding_transcript_exon_variant Exon 4 of 8 1
SFT2D1ENST00000478705.5 linkn.297G>T non_coding_transcript_exon_variant Exon 4 of 9 2
SFT2D1ENST00000488773.1 linkn.139G>T non_coding_transcript_exon_variant Exon 3 of 6 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1456186
Hom.:
0
Cov.:
30
AF XY:
0.00000414
AC XY:
3
AN XY:
724406
show subpopulations
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:
0.00000271
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 13, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.179G>T (p.G60V) alteration is located in exon 3 (coding exon 3) of the SFT2D1 gene. This alteration results from a G to T substitution at nucleotide position 179, causing the glycine (G) at amino acid position 60 to be replaced by a valine (V). 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
0.88
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.060
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.060
T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.014
T
MetaRNN
Pathogenic
0.86
D
MetaSVM
Benign
-0.74
T
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-5.8
D
REVEL
Uncertain
0.41
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.88
MutPred
0.66
Loss of sheet (P = 0.0054);
MVP
0.69
MPC
0.39
ClinPred
1.0
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.90
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chr6-166743049; API