rs1002922620

Variant names:

• chr15-34038856-C-A
• rs1002922620
• NM_020371.3:c.191G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-34038856-C-A
• chr15-34038856-C-G
• chr15-34038856-C-T

Variant summary

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

The NM_020371.3(AVEN):​c.191G>T​(p.Gly64Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000991 in 1,008,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G64E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.9e-7 (0 hom.)
• Consequence: AVEN NM_020371.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 0 publications found

Genes affected

AVEN (HGNC:13509): (apoptosis and caspase activation inhibitor) Involved in negative regulation of apoptotic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CHRM5 (HGNC:1954): (cholinergic receptor muscarinic 5) The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The clinical implications of this receptor are unknown; however, stimulation of this receptor is known to increase cyclic AMP levels. [provided by RefSeq, Jul 2008]

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=0.21191177).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020371.3. 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
	AVEN	NM_020371.3	MANE Select	c.191G>T	p.Gly64Val	missense	Exon 1 of 6	NP_065104.1	Q9NQS1
	CHRM5	NM_012125.4	MANE Select	c.-407-7684C>A		intron	N/A	NP_036257.1	P08912
	CHRM5	NM_001320917.2		c.-75-23787C>A		intron	N/A	NP_001307846.1	P08912

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVEN	ENST00000306730.8	TSL:1 MANE Select	c.191G>T	p.Gly64Val	missense	Exon 1 of 6	ENSP00000306822.3	Q9NQS1
	CHRM5	ENST00000383263.7	TSL:2 MANE Select	c.-407-7684C>A		intron	N/A	ENSP00000372750.5	P08912
	CHRM5	ENST00000557872.1	TSL:1	c.-76+20391C>A		intron	N/A	ENSP00000453745.1	P08912

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.91e-7 AC: 1 AN: 1008608 Hom.: 0 Cov.: 29 AF XY: 0.00000209 AC XY: 1 AN XY: 478624

African (AFR) AF: 0.00 AC: 0 AN: 19418

American (AMR) AF: 0.00 AC: 0 AN: 6264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10510

East Asian (EAS) AF: 0.00 AC: 0 AN: 18198

South Asian (SAS) AF: 0.00 AC: 0 AN: 20056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2476

European-Non Finnish (NFE) AF: 0.00000114 AC: 1 AN: 877322

Other (OTH) AF: 0.00 AC: 0 AN: 37672

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.30	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.4
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.030
Sift	Benign	0.16	T
Sift4G	Uncertain	0.022	D
Polyphen		0.92	P
Vest4		0.18
MutPred		0.37		Gain of sheet (P = 0.0085)
MVP		0.68
MPC		0.00098
ClinPred		0.72	D
GERP RS		2.1
PromoterAI		0.22	Neutral
Varity_R		0.092
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1002922620; hg19: chr15-34331057;