11-9724872-A-G

Variant names:

• chr11-9724872-A-G
• NM_015055.4:c.629A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015055.4(SWAP70):​c.629A>G​(p.Asp210Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,448,740 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SWAP70 NM_015055.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.28

Genes affected

SWAP70 (HGNC:17070): (switching B cell complex subunit SWAP70) Enables cadherin binding activity. Predicted to be involved in regulation of actin polymerization or depolymerization. Predicted to act upstream of or within isotype switching. Located in actin cytoskeleton; cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SWAP70	NM_015055.4	c.629A>G	p.Asp210Gly	missense_variant	Exon 4 of 12	ENST00000318950.11	NP_055870.2
SWAP70	NM_001297714.2	c.455A>G	p.Asp152Gly	missense_variant	Exon 3 of 11		NP_001284643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SWAP70	ENST00000318950.11	c.629A>G	p.Asp210Gly	missense_variant	Exon 4 of 12	1	NM_015055.4	ENSP00000315630.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000414 AC: 6 AN: 1448740 Hom.: 0 Cov.: 28 AF XY: 0.00000555 AC XY: 4 AN XY: 721188

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000545

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.629A>G (p.D210G) alteration is located in exon 4 (coding exon 4) of the SWAP70 gene. This alteration results from a A to G substitution at nucleotide position 629, causing the aspartic acid (D) at amino acid position 210 to be replaced by a glycine (G). 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	Uncertain	0.46
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	.;D;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.2	.;M;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.0	D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.91
MutPred		0.49		.;Loss of stability (P = 0.0451);.;
MVP		0.43
MPC		1.3
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.67
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-9746419;