2-127701943-G-A

Position:

chr2-127701943-G-A

Variant summary

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

The NM_032740.4(SFT2D3):c.415G>A(p.Glu139Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000107 in 1,416,598 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

SFT2D3
NM_032740.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63

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:

Genome browser will be placed here

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=0.09177813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SFT2D3	NM_032740.4 linkuse as main transcript	c.415G>A	p.Glu139Lys	missense_variant	1/1	ENST00000310981.6
WDR33	NM_018383.5 linkuse as main transcript	c.*4380C>T		3_prime_UTR_variant	22/22	ENST00000322313.9
WDR33	XM_005263697.4 linkuse as main transcript	c.*4550C>T		3_prime_UTR_variant	21/21
WDR33	XM_011511436.2 linkuse as main transcript	c.*4380C>T		3_prime_UTR_variant	22/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFT2D3	ENST00000310981.6 linkuse as main transcript	c.415G>A	p.Glu139Lys	missense_variant	1/1		NM_032740.4	P1
WDR33	ENST00000322313.9 linkuse as main transcript	c.*4380C>T		3_prime_UTR_variant	22/22	1	NM_018383.5	P1	Q9C0J8-1

Frequencies

GnomAD3 genomes

AF:

0.0000796

AC:

AN:

150734

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:

0.000178

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000117

AC:

AN:

42602

Hom.:

AF XY:

0.0000389

AC XY:

AN XY:

25696

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000147

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:

0.000239

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000110

AC:

139

AN:

1265756

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

623112

show subpopulations

Gnomad4 AFR exome

AF:

0.0000405

Gnomad4 AMR exome

AF:

0.000117

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:

0.000119

Gnomad4 OTH exome

AF:

0.000270

GnomAD4 genome

AF:

0.0000796

AC:

AN:

150842

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73694

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000178

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000774

AC:

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 submitter

clinical testing

Ambry Genetics

Aug 10, 2023

The c.415G>A (p.E139K) alteration is located in exon 1 (coding exon 1) of the SFT2D3 gene. This alteration results from a G to A substitution at nucleotide position 415, causing the glutamic acid (E) at amino acid position 139 to be replaced by a lysine (K). 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

0.20

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0037

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.65

M_CAP

Benign

0.054

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.59

REVEL

Benign

0.097

Sift

Benign

0.82

Sift4G

Benign

0.64

Polyphen

0.82

Vest4

0.34

MutPred

0.61

Gain of methylation at E139 (P = 0.0134);

MVP

0.40

ClinPred

0.23

GERP RS

1.6

Varity_R

0.11

gMVP

0.34

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