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GeneBe

10-103602380-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001394015.1(SH3PXD2A):c.2838G>A(p.Thr946=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,613,746 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 12 hom., cov: 33)
Exomes 𝑓: 0.00082 ( 18 hom. )

Consequence

SH3PXD2A
NM_001394015.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.01
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-103602380-C-T is Benign according to our data. Variant chr10-103602380-C-T is described in ClinVar as [Benign]. Clinvar id is 776537.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.01 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0078 (1187/152276) while in subpopulation AFR AF= 0.0275 (1141/41546). AF 95% confidence interval is 0.0261. There are 12 homozygotes in gnomad4. There are 591 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1190 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SH3PXD2ANM_001394015.1 linkuse as main transcriptc.2838G>A p.Thr946= synonymous_variant 15/15 ENST00000369774.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SH3PXD2AENST00000369774.9 linkuse as main transcriptc.2838G>A p.Thr946= synonymous_variant 15/155 NM_001394015.1 P4Q5TCZ1-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00782
AC:
1190
AN:
152158
Hom.:
13
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0276
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00209
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00318
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00479
GnomAD3 exomes
AF:
0.00195
AC:
487
AN:
249740
Hom.:
6
AF XY:
0.00138
AC XY:
187
AN XY:
135114
show subpopulations
Gnomad AFR exome
AF:
0.0276
Gnomad AMR exome
AF:
0.000898
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:
0.0000267
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.000819
AC:
1197
AN:
1461470
Hom.:
18
Cov.:
63
AF XY:
0.000708
AC XY:
515
AN XY:
727010
show subpopulations
Gnomad4 AFR exome
AF:
0.0307
Gnomad4 AMR exome
AF:
0.000939
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000243
Gnomad4 OTH exome
AF:
0.00151
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00780
AC:
1187
AN:
152276
Hom.:
12
Cov.:
33
AF XY:
0.00794
AC XY:
591
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0275
Gnomad4 AMR
AF:
0.00209
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00474
Alfa
AF:
0.00387
Hom.:
6
Bravo
AF:
0.00900
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 06, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
2.6
Dann
Benign
0.64

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.

Other links and lift over

dbSNP: rs115149308; hg19: chr10-105362137; API