15-34038932-C-T

Variant names:

• chr15-34038932-C-T
• rs1319346116
• NM_020371.3:c.115G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020371.3(AVEN):​c.115G>A​(p.Gly39Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000724 in 1,104,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: AVEN NM_020371.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0830
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.239306).

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.115G>A	p.Gly39Ser	missense	Exon 1 of 6	NP_065104.1	Q9NQS1
	CHRM5	NM_012125.4	MANE Select	c.-407-7608C>T		intron	N/A	NP_036257.1	P08912
	CHRM5	NM_001320917.2		c.-75-23711C>T		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.115G>A	p.Gly39Ser	missense	Exon 1 of 6	ENSP00000306822.3	Q9NQS1
	CHRM5	ENST00000383263.7	TSL:2 MANE Select	c.-407-7608C>T		intron	N/A	ENSP00000372750.5	P08912
	CHRM5	ENST00000557872.1	TSL:1	c.-76+20467C>T		intron	N/A	ENSP00000453745.1	P08912

Frequencies

GnomAD3 genomes AF: 0.0000404 AC: 6 AN: 148428 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000334

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: 0.00

Gnomad OTH AF: 0.000489

GnomAD2 exomes AF: 0.00 AC: 0 AN: 2024 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000209 AC: 2 AN: 956284 Hom.: 0 Cov.: 31 AF XY: 0.00000441 AC XY: 2 AN XY: 453112

African (AFR) AF: 0.00 AC: 0 AN: 18316

American (AMR) AF: 0.000413 AC: 2 AN: 4840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8904

East Asian (EAS) AF: 0.00 AC: 0 AN: 11418

South Asian (SAS) AF: 0.00 AC: 0 AN: 19298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2246

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 844044

Other (OTH) AF: 0.00 AC: 0 AN: 34558

GnomAD4 genome AF: 0.0000404 AC: 6 AN: 148428 Hom.: 0 Cov.: 33 AF XY: 0.0000415 AC XY: 3 AN XY: 72322

African (AFR) AF: 0.00 AC: 0 AN: 41028

American (AMR) AF: 0.000334 AC: 5 AN: 14950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3404

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66550

Other (OTH) AF: 0.000489 AC: 1 AN: 2046

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.022
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.33	T
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.083
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	0.14	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.23
MutPred		0.28		Gain of phosphorylation at G39 (P = 9e-04)
MVP		0.49
MPC		0.0012
ClinPred		0.91	D
GERP RS		1.2
PromoterAI		-0.071	Neutral
Varity_R		0.12
gMVP		0.093

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: rs1319346116; hg19: chr15-34331133;