NM_053004.3:c.836T>C

Variant names:

• chr22-19788857-A-G
• rs867982105
• NM_053004.3:c.836T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_053004.3(GNB1L):​c.836T>C​(p.Val279Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,460,506 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V279M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: GNB1L NM_053004.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 8.65
• Publications: 1 publications found

Genes affected

GNB1L (HGNC:4397): (G protein subunit beta 1 like) This gene encodes a G-protein beta-subunit-like polypeptide which is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 6 WD repeats and is highly expressed in the heart. The gene maps to the region on chromosome 22q11, which is deleted in DiGeorge syndrome, trisomic in derivative 22 syndrome and tetrasomic in cat-eye syndrome. Therefore, this gene may contribute to the etiology of those disorders. Transcripts from this gene share exons with some transcripts from the C22orf29 gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 22-19788857-A-G is Benign according to our data. Variant chr22-19788857-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 388873.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053004.3. 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
	GNB1L	NM_053004.3	MANE Select	c.836T>C	p.Val279Ala	missense	Exon 8 of 8	NP_443730.1	Q9BYB4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB1L	ENST00000329517.11	TSL:1 MANE Select	c.836T>C	p.Val279Ala	missense	Exon 8 of 8	ENSP00000331313.6	Q9BYB4-1
	GNB1L	ENST00000403325.5	TSL:1	c.836T>C	p.Val279Ala	missense	Exon 7 of 7	ENSP00000385154.1	Q9BYB4-1
	GNB1L	ENST00000405009.5	TSL:1	c.631-231T>C		intron	N/A	ENSP00000384626.1	Q9BYB4-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1460506 Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6 AN XY: 726586

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52268

Middle Eastern (MID) AF: 0.00279 AC: 16 AN: 5732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111922

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	0.038	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		8.7
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.49
MutPred		0.62		Loss of stability (P = 0.0585)
MVP		0.78
MPC		0.60
ClinPred		0.79	D
GERP RS		5.5
Varity_R		0.29
gMVP		0.39
Mutation Taster		=61/39	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: rs867982105; hg19: chr22-19776380;