Genetic Variant SFT2D3:p.Leu86Gln (chr2-127701785-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032740.4(SFT2D3):c.257T>A(p.Leu86Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000459 in 1,445,710 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00046 ( 1 hom. )

Consequence

SFT2D3
NM_032740.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.75

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013540357).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032740.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFT2D3	NM_032740.4	MANE Select	c.257T>A	p.Leu86Gln	missense	Exon 1 of 1	NP_116129.3
	WDR33	NM_018383.5	MANE Select	c.*4538A>T		3_prime_UTR	Exon 22 of 22	NP_060853.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFT2D3	ENST00000310981.6	TSL:6 MANE Select	c.257T>A	p.Leu86Gln	missense	Exon 1 of 1	ENSP00000310803.3	Q587I9
	WDR33	ENST00000322313.9	TSL:1 MANE Select	c.*4538A>T		3_prime_UTR	Exon 22 of 22	ENSP00000325377.3	Q9C0J8-1

Frequencies

GnomAD3 genomes

AF:

0.000465

AC:

AN:

150536

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

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:

0.000728

Gnomad OTH

AF:

0.000484

GnomAD2 exomes

AF:

0.000523

AC:

AN:

74570

AF XY:

0.000441

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.000152

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000697

Gnomad OTH exome

AF:

0.00140

GnomAD4 exome

AF:

0.000459

AC:

594

AN:

1295066

Hom.:

Cov.:

AF XY:

0.000441

AC XY:

282

AN XY:

639022

show subpopulations

African (AFR)

AF:

0.0000382

AC:

AN:

26160

American (AMR)

AF:

0.00114

AC:

AN:

24634

Ashkenazi Jewish (ASJ)

AF:

0.0000448

AC:

AN:

22342

East Asian (EAS)

AF:

0.00

AC:

AN:

26862

South Asian (SAS)

AF:

0.00

AC:

AN:

71440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32300

Middle Eastern (MID)

AF:

0.000775

AC:

AN:

3870

European-Non Finnish (NFE)

AF:

0.000521

AC:

539

AN:

1034450

Other (OTH)

AF:

0.000415

AC:

AN:

53008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

119

159

199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000465

AC:

AN:

150644

Hom.:

Cov.:

AF XY:

0.000530

AC XY:

AN XY:

73550

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41422

American (AMR)

AF:

0.00112

AC:

AN:

15162

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000728

AC:

AN:

67272

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000582

Hom.:

Bravo

AF:

0.000491

ExAC

AF:

0.000171

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.72

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.5

PhyloP100

2.7

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.3

REVEL

Benign

0.23

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.059

Polyphen

1.0

Vest4

0.55

MVP

0.73

ClinPred

0.054

GERP RS

3.8

PromoterAI

-0.052

Neutral

(source)

Varity_R

0.60

gMVP

0.51

Mutation Taster

=50/50

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over