Genetic Variant SFT2D1:p.Gly71Asp (chr6-166329528-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_145169.3(SFT2D1):c.212G>A(p.Gly71Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,084 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G71S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SFT2D1
NM_145169.3 missense

Scores

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]

SFT2D1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFT2D1	NM_145169.3 link	c.212G>A	p.Gly71Asp	missense_variant	Exon 3 of 8	ENST00000361731.4	NP_660152.1	Q8WV19
SFT2D1	NR_130112.2 link	n.299G>A		non_coding_transcript_exon_variant	Exon 4 of 9
SFT2D1	NR_130113.2 link	n.299G>A		non_coding_transcript_exon_variant	Exon 4 of 7
SFT2D1	NR_130114.2 link	n.290G>A		non_coding_transcript_exon_variant	Exon 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SFT2D1	ENST00000361731.4 link	c.212G>A	p.Gly71Asp	missense_variant	Exon 3 of 8	1	NM_145169.3	ENSP00000354590.3	Q8WV19
SFT2D1	ENST00000487841.5 link	n.301G>A		non_coding_transcript_exon_variant	Exon 4 of 8	1
SFT2D1	ENST00000478705.5 link	n.330G>A		non_coding_transcript_exon_variant	Exon 4 of 9	2
SFT2D1	ENST00000488773.1 link	n.172G>A		non_coding_transcript_exon_variant	Exon 3 of 6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251276

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135810

show subpopulations

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457084

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724852

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 30, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.212G>A (p.G71D) alteration is located in exon 3 (coding exon 3) of the SFT2D1 gene. This alteration results from a G to A substitution at nucleotide position 212, causing the glycine (G) at amino acid position 71 to be replaced by an aspartic acid (D). 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

1.0

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.048

MetaRNN

Pathogenic

0.95

MetaSVM

Uncertain

0.63

MutationAssessor

Pathogenic

3.7

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-6.5

REVEL

Pathogenic

0.79

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.95

MutPred

0.82

Gain of sheet (P = 0.0016);

MVP

0.82

MPC

0.76

ClinPred

1.0

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.97

gMVP

0.98

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over