2-127701590-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032740.4(SFT2D3):c.62C>A(p.Ala21Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,330,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 34)

Exomes 𝑓: 8.5e-7 ( 0 hom. )

Consequence

SFT2D3
NM_032740.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.364

Publications

0 publications found

Variant links:

Genes affected

SFT2D3 (HGNC:28767): (SFT2 domain containing 3) 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]

SFT2D3 links:

WDR33 (HGNC:25651): (WD repeat domain 33) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is highly expressed in testis and the protein is localized to the nucleus. This gene may play important roles in the mechanisms of cytodifferentiation and/or DNA recombination. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

WDR33 links:

ENSG00000293688 (HGNC:):

ENSG00000293688 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.070028335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFT2D3	NM_032740.4 link	c.62C>A	p.Ala21Glu	missense_variant	Exon 1 of 1	ENST00000310981.6	NP_116129.3	Q587I9
WDR33	NM_018383.5 link	c.*4733G>T		3_prime_UTR_variant	Exon 22 of 22	ENST00000322313.9	NP_060853.3	Q9C0J8-1
WDR33	XM_011511436.2 link	c.*4733G>T		3_prime_UTR_variant	Exon 22 of 22		XP_011509738.1	Q9C0J8-1
WDR33	XM_005263697.4 link	c.*4903G>T		3_prime_UTR_variant	Exon 21 of 21		XP_005263754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SFT2D3	ENST00000310981.6 link	c.62C>A	p.Ala21Glu	missense_variant	Exon 1 of 1	6	NM_032740.4	ENSP00000310803.3	Q587I9
WDR33	ENST00000322313.9 link	c.*4733G>T		3_prime_UTR_variant	Exon 22 of 22	1	NM_018383.5	ENSP00000325377.3	Q9C0J8-1
ENSG00000293688	ENST00000718293.1 link	n.-130G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.00000668

AC:

AN:

149714

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000294

AC:

AN:

34024

AF XY:

0.0000501

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000399

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

8.47e-7

AC:

AN:

1180896

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

577934

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24172

American (AMR)

AF:

0.00

AC:

AN:

13588

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17014

East Asian (EAS)

AF:

0.00

AC:

AN:

27044

South Asian (SAS)

AF:

0.00

AC:

AN:

50672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3110

European-Non Finnish (NFE)

AF:

0.00000103

AC:

AN:

966884

Other (OTH)

AF:

0.00

AC:

AN:

47188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000668

AC:

AN:

149714

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73190

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41286

American (AMR)

AF:

0.00

AC:

AN:

15064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3256

East Asian (EAS)

AF:

0.00

AC:

AN:

5062

South Asian (SAS)

AF:

0.00

AC:

AN:

4722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66780

Other (OTH)

AF:

0.00

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000221

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 04, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.62C>A (p.A21E) alteration is located in exon 1 (coding exon 1) of the SFT2D3 gene. This alteration results from a C to A substitution at nucleotide position 62, causing the alanine (A) at amino acid position 21 to be replaced by a glutamic acid (E). 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

Benign

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0042

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.41

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

0.36

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.53

REVEL

Benign

0.037

Sift

Benign

0.53

Sift4G

Benign

0.071

Polyphen

0.70

Vest4

0.12

MutPred

0.11

Gain of methylation at K16 (P = 0.1051);

MVP

0.56

ClinPred

0.19

GERP RS

0.90

PromoterAI

0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.10

gMVP

0.38

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-127701590-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over