chr19-41877368-T-A

Variant names:

• chr19-41877368-T-A
• rs1600629998
• NM_001783.4:c.64T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001783.4(CD79A):​c.64T>A​(p.Ser22Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD79A NM_001783.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.634
• Publications: 0 publications found

Genes affected

CD79A (HGNC:1698): (CD79a molecule) The B lymphocyte antigen receptor is a multimeric complex that includes the antigen-specific component, surface immunoglobulin (Ig). Surface Ig non-covalently associates with two other proteins, Ig-alpha and Ig-beta, which are necessary for expression and function of the B-cell antigen receptor. This gene encodes the Ig-alpha protein of the B-cell antigen component. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

CD79A Gene-Disease associations (from GenCC):

• agammaglobulinemia 3, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• autosomal agammaglobulinemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22347587).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001783.4. 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
	CD79A	NM_001783.4	MANE Select	c.64T>A	p.Ser22Thr	missense	Exon 1 of 5	NP_001774.1	P11912-1
	CD79A	NM_021601.4		c.64T>A	p.Ser22Thr	missense	Exon 1 of 5	NP_067612.1	P11912-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD79A	ENST00000221972.8	TSL:1 MANE Select	c.64T>A	p.Ser22Thr	missense	Exon 1 of 5	ENSP00000221972.3	P11912-1
	CD79A	ENST00000444740.2	TSL:1	c.64T>A	p.Ser22Thr	missense	Exon 1 of 5	ENSP00000400605.1	P11912-2
	CD79A	ENST00000597454.2	TSL:3	c.64T>A	p.Ser22Thr	missense	Exon 1 of 4	ENSP00000468922.2	M0QX61

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Agammaglobulinemia 3, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.63
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.26
Sift	Benign	0.063	T
Sift4G	Benign	0.47	T
Polyphen		0.99	D
Vest4		0.31
MutPred		0.54		Loss of sheet (P = 0.007)
MVP		0.73
MPC		0.84
ClinPred		0.53	D
GERP RS		1.4
PromoterAI		0.031	Neutral
Varity_R		0.079
gMVP		0.47
Mutation Taster		=92/8	polymorphism

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: rs1600629998; hg19: chr19-42381438;