chr6-166320236-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145169.3(SFT2D1):​c.461G>A​(p.Cys154Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SFT2D1
NM_145169.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.878
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]

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ACMG classification

Classification made for transcript

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=0.1887115).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFT2D1NM_145169.3 linkuse as main transcriptc.461G>A p.Cys154Tyr missense_variant 8/8 ENST00000361731.4
SFT2D1NR_130112.2 linkuse as main transcriptn.548G>A non_coding_transcript_exon_variant 9/9
SFT2D1NR_130113.2 linkuse as main transcriptn.453G>A non_coding_transcript_exon_variant 7/7
SFT2D1NR_130114.2 linkuse as main transcriptn.444G>A non_coding_transcript_exon_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFT2D1ENST00000361731.4 linkuse as main transcriptc.461G>A p.Cys154Tyr missense_variant 8/81 NM_145169.3 P1
SFT2D1ENST00000479490.1 linkuse as main transcriptn.1853G>A non_coding_transcript_exon_variant 2/21
SFT2D1ENST00000487841.5 linkuse as main transcriptn.2200G>A non_coding_transcript_exon_variant 8/81
SFT2D1ENST00000478705.5 linkuse as main transcriptn.579G>A non_coding_transcript_exon_variant 9/92

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000343
AC:
5
AN:
1459366
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
725918
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.0000226
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:
0.00000270
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 05, 2022The c.461G>A (p.C154Y) alteration is located in exon 8 (coding exon 8) of the SFT2D1 gene. This alteration results from a G to A substitution at nucleotide position 461, causing the cysteine (C) at amino acid position 154 to be replaced by a tyrosine (Y). 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
Uncertain
0.44
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
22
DANN
Benign
0.61
DEOGEN2
Benign
0.018
T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.23
FATHMM_MKL
Benign
0.71
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.5
M
MutationTaster
Benign
0.98
D
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
0.39
N
REVEL
Benign
0.14
Sift
Benign
0.030
D
Sift4G
Benign
0.075
T
Polyphen
0.52
P
Vest4
0.50
MutPred
0.42
Gain of disorder (P = 0.0666);
MVP
0.076
MPC
0.60
ClinPred
0.76
D
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.13
gMVP
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1223752762; hg19: chr6-166733724; API