rs532288711

Variant names:

• chr19-41880892-T-C
• rs532288711
• NM_001783.4:c.593T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001783.4(CD79A):​c.593T>C​(p.Met198Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00027 in 1,605,722 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00029 (1 hom.)
• Consequence: CD79A NM_001783.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:1
• Conservation: PhyloP100: 4.17
• Publications: 3 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3444494).

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.593T>C	p.Met198Thr	missense	Exon 5 of 5	NP_001774.1
	CD79A	NM_021601.4		c.479T>C	p.Met160Thr	missense	Exon 5 of 5	NP_067612.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD79A	ENST00000221972.8	TSL:1 MANE Select	c.593T>C	p.Met198Thr	missense	Exon 5 of 5	ENSP00000221972.3
	CD79A	ENST00000444740.2	TSL:1	c.479T>C	p.Met160Thr	missense	Exon 5 of 5	ENSP00000400605.1
	CD79A	ENST00000597454.2	TSL:3	c.*19T>C		3_prime_UTR	Exon 4 of 4	ENSP00000468922.2

Frequencies

GnomAD3 genomes AF: 0.000119 AC: 18 AN: 151870 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000149 AC: 35 AN: 235186 AF XY: 0.000158

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000321

Gnomad OTH exome AF: 0.000173

GnomAD4 exome AF: 0.000286 AC: 416 AN: 1453734 Hom.: 1 Cov.: 31 AF XY: 0.000274 AC XY: 198 AN XY: 722200

African (AFR) AF: 0.0000299 AC: 1 AN: 33416

American (AMR) AF: 0.0000229 AC: 1 AN: 43632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25808

East Asian (EAS) AF: 0.00 AC: 0 AN: 39478

South Asian (SAS) AF: 0.00 AC: 0 AN: 84200

European-Finnish (FIN) AF: 0.0000380 AC: 2 AN: 52640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000367 AC: 407 AN: 1108682

Other (OTH) AF: 0.0000832 AC: 5 AN: 60120

GnomAD4 genome AF: 0.000118 AC: 18 AN: 151988 Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5 AN XY: 74286

African (AFR) AF: 0.0000241 AC: 1 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67924

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000259 Hom.: 0

Bravo AF: 0.000174

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.000181 AC: 22

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Agammaglobulinemia 3, autosomal recessive (1)
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.0037
Eigen_PC	Benign	0.063
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.2
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.18
Sift	Benign	0.79	T
Sift4G	Benign	0.57	T
Polyphen		0.66	P
Vest4		0.67
MVP		0.51
MPC		1.3
ClinPred		0.10	T
GERP RS		3.7
Varity_R		0.10
gMVP		0.44
Mutation Taster		=85/15	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: rs532288711; hg19: chr19-42384959; COSMIC: COSV105819776;