19-41879044-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001783.4(CD79A):c.134G>C(p.Ser45Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000973 in 1,613,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000082 (0 hom.)
• Consequence: CD79A NM_001783.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:4
• Conservation: PhyloP100: -1.07

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.015384376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD79A	NM_001783.4	c.134G>C	p.Ser45Thr	missense_variant	2/5	ENST00000221972.8
CD79A	NM_021601.4	c.134G>C	p.Ser45Thr	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD79A	ENST00000221972.8	c.134G>C	p.Ser45Thr	missense_variant	2/5	1	NM_001783.4	P1
CD79A	ENST00000444740.2	c.134G>C	p.Ser45Thr	missense_variant	2/5	1
CD79A	ENST00000597454.2	c.134G>C	p.Ser45Thr	missense_variant	2/4	3

Frequencies

GnomAD3 genomes AF: 0.000244 AC: 37 AN: 151888 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000147 AC: 37 AN: 250858 Hom.: 0 AF XY: 0.000103 AC XY: 14 AN XY: 135724

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000694

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: 0.0000970

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.0000821 AC: 120 AN: 1461064 Hom.: 0 Cov.: 36 AF XY: 0.0000715 AC XY: 52 AN XY: 726840

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000716

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: 0.0000702

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152006 Hom.: 0 Cov.: 31 AF XY: 0.000202 AC XY: 15 AN XY: 74320

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000589

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.0000596 Hom.: 0

Bravo AF: 0.000385

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Agammaglobulinemia 3, autosomal recessive Uncertain:4

Uncertain significance, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Apr 05, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	New York Genome Center	Oct 07, 2021	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Invitae	Oct 05, 2022	This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 45 of the CD79A protein (p.Ser45Thr). This variant is present in population databases (rs199603062, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with CD79A-related conditions. ClinVar contains an entry for this variant (Variation ID: 839358). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Uncertain significance, criteria provided, single submitter	clinical testing	Baylor Genetics	Jul 31, 2018	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	0.11
Dann	Benign	0.50
DEOGEN2	Benign	0.35	T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.31	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.015	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M;.;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N;.;N
REVEL	Benign	0.18
Sift	Benign	0.16	T;.;T
Sift4G	Benign	0.55	T;T;T
Polyphen		0.80	P;.;.
Vest4		0.15
MVP		0.65
MPC		0.46
ClinPred		0.095	T
GERP RS		-10
Varity_R		0.050
gMVP		0.43

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

Other links and lift over

dbSNP: rs199603062; hg19: chr19-42383114;