10-103602114-C-T

Variant names:

• chr10-103602114-C-T
• rs3781365
• NM_001394015.1:c.3104G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001394015.1(SH3PXD2A):​c.3104G>A​(p.Arg1035Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,587,978 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (33 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (179 hom.)
• Consequence: SH3PXD2A NM_001394015.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.23
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014967918).
• BP6: Variant 10-103602114-C-T is Benign according to our data. Variant chr10-103602114-C-T is described in ClinVar as Benign. ClinVar VariationId is 708369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3PXD2A	NM_001394015.1	MANE Select	c.3104G>A	p.Arg1035Gln	missense	Exon 15 of 15	NP_001380944.1
	SH3PXD2A	NM_014631.3		c.3020G>A	p.Arg1007Gln	missense	Exon 14 of 14	NP_055446.2
	SH3PXD2A	NM_001365079.1		c.2747G>A	p.Arg916Gln	missense	Exon 9 of 9	NP_001352008.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3PXD2A	ENST00000369774.9	TSL:5 MANE Select	c.3104G>A	p.Arg1035Gln	missense	Exon 15 of 15	ENSP00000358789.4
	SH3PXD2A	ENST00000355946.7	TSL:1	c.3020G>A	p.Arg1007Gln	missense	Exon 14 of 14	ENSP00000348215.2
	SH3PXD2A	ENST00000315994.6	TSL:1	n.2910G>A		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 775 AN: 152198 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.00848

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00921 AC: 2146 AN: 232890 AF XY: 0.00819

Gnomad AFR exome AF: 0.000752

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.00120

Gnomad EAS exome AF: 0.0988

Gnomad FIN exome AF: 0.00798

Gnomad NFE exome AF: 0.000634

Gnomad OTH exome AF: 0.00495

GnomAD4 exome AF: 0.00335 AC: 4807 AN: 1435662 Hom.: 179 Cov.: 63 AF XY: 0.00328 AC XY: 2327 AN XY: 710332

African (AFR) AF: 0.000364 AC: 12 AN: 32932

American (AMR) AF: 0.00180 AC: 77 AN: 42804

Ashkenazi Jewish (ASJ) AF: 0.000489 AC: 12 AN: 24546

East Asian (EAS) AF: 0.0936 AC: 3682 AN: 39332

South Asian (SAS) AF: 0.00117 AC: 96 AN: 82256

European-Finnish (FIN) AF: 0.00725 AC: 380 AN: 52394

Middle Eastern (MID) AF: 0.000531 AC: 3 AN: 5650

European-Non Finnish (NFE) AF: 0.000205 AC: 225 AN: 1096588

Other (OTH) AF: 0.00541 AC: 320 AN: 59160

GnomAD4 genome AF: 0.00508 AC: 774 AN: 152316 Hom.: 33 Cov.: 33 AF XY: 0.00600 AC XY: 447 AN XY: 74480

African (AFR) AF: 0.000842 AC: 35 AN: 41574

American (AMR) AF: 0.00379 AC: 58 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.102 AC: 528 AN: 5184

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4824

European-Finnish (FIN) AF: 0.00848 AC: 90 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.270 Hom.: 6743

Bravo AF: 0.00496

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00814 AC: 987

Asia WGS AF: 0.0280 AC: 98 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.2
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.20
Sift	Uncertain	0.016	D
Sift4G	Benign	0.48	T
Polyphen		1.0	D
Vest4		0.077
MVP		0.68
MPC		1.2
ClinPred		0.014	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.24
gMVP		0.64
Mutation Taster		=74/26	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3781365; hg19: chr10-105361871; COSMIC: COSV60117616;