Genetic Variant NM_001394015.1:c.2993G>A (chr10-103602225-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001394015.1(SH3PXD2A):c.2993G>A(p.Arg998Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00014 in 1,597,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SH3PXD2A
NM_001394015.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

Publications

3 publications found

Variant links:

Genes affected

SH3PXD2A (HGNC:23664): (SH3 and PX domains 2A) Predicted to enable superoxide-generating NADPH oxidase activator activity. Involved in osteoclast fusion and superoxide metabolic process. Located in podosome. [provided by Alliance of Genome Resources, Apr 2022]

SH3PXD2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.37955394).

BS2

High AC in GnomAd4 at 17 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394015.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3PXD2A	NM_001394015.1	MANE Select	c.2993G>A	p.Arg998Gln	missense	Exon 15 of 15	NP_001380944.1	Q5TCZ1-1
SH3PXD2A	NM_014631.3		c.2909G>A	p.Arg970Gln	missense	Exon 14 of 14	NP_055446.2
SH3PXD2A	NM_001365079.1		c.2636G>A	p.Arg879Gln	missense	Exon 9 of 9	NP_001352008.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3PXD2A	ENST00000369774.9	TSL:5 MANE Select	c.2993G>A	p.Arg998Gln	missense	Exon 15 of 15	ENSP00000358789.4	Q5TCZ1-1
SH3PXD2A	ENST00000355946.7	TSL:1	c.2909G>A	p.Arg970Gln	missense	Exon 14 of 14	ENSP00000348215.2	Q5TCZ1-3
SH3PXD2A	ENST00000315994.6	TSL:1	n.2799G>A		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000157

AC:

AN:

235434

AF XY:

0.000158

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000199

Gnomad OTH exome

AF:

0.000526

GnomAD4 exome

AF:

0.000143

AC:

206

AN:

1445342

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

106

AN XY:

717056

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33176

American (AMR)

AF:

0.0000230

AC:

AN:

43548

Ashkenazi Jewish (ASJ)

AF:

0.0000404

AC:

AN:

24780

East Asian (EAS)

AF:

0.00

AC:

AN:

39536

South Asian (SAS)

AF:

0.000204

AC:

AN:

83158

European-Finnish (FIN)

AF:

0.000114

AC:

AN:

52670

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.000154

AC:

170

AN:

1103192

Other (OTH)

AF:

0.000168

AC:

AN:

59588

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000112

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41418

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

0.000220

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000148

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

Uncertain

0.52

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.021

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.074

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.0

PhyloP100

5.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.3

REVEL

Benign

0.17

Sift

Benign

0.062

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.49

MVP

0.80

MPC

1.2

ClinPred

0.13

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.50

Mutation Taster

=63/37

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.

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