19-17323734-C-A

Variant names:

• chr19-17323734-C-A
• rs911115787
• NM_020959.3:c.3482G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_020959.3(ANO8):​c.3482G>T​(p.Gly1161Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,204,766 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: ANO8 NM_020959.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.254
• Publications: 0 publications found

Genes affected

ANO8 (HGNC:29329): (anoctamin 8) Enables intracellular calcium activated chloride channel activity. Involved in chloride transport. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08593598).
• BS2: High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020959.3. 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
	ANO8	NM_020959.3	MANE Select	c.3482G>T	p.Gly1161Val	missense	Exon 18 of 18	NP_066010.1	Q9HCE9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO8	ENST00000159087.7	TSL:1 MANE Select	c.3482G>T	p.Gly1161Val	missense	Exon 18 of 18	ENSP00000159087.4	Q9HCE9-1
	ANO8	ENST00000597643.5	TSL:2	n.*2294G>T		non_coding_transcript_exon	Exon 18 of 18	ENSP00000469751.1	M0QYD2
	ANO8	ENST00000597643.5	TSL:2	n.*2294G>T		3_prime_UTR	Exon 18 of 18	ENSP00000469751.1	M0QYD2

Frequencies

GnomAD3 genomes AF: 0.0000531 AC: 8 AN: 150680 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

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: 0.000119

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000225 AC: 237 AN: 1054086 Hom.: 0 Cov.: 31 AF XY: 0.000223 AC XY: 111 AN XY: 497634

African (AFR) AF: 0.00 AC: 0 AN: 21860

American (AMR) AF: 0.00 AC: 0 AN: 7674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13226

East Asian (EAS) AF: 0.00 AC: 0 AN: 25120

South Asian (SAS) AF: 0.00 AC: 0 AN: 19250

European-Finnish (FIN) AF: 0.0000995 AC: 2 AN: 20100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2792

European-Non Finnish (NFE) AF: 0.000253 AC: 228 AN: 902260

Other (OTH) AF: 0.000167 AC: 7 AN: 41804

GnomAD4 genome AF: 0.0000531 AC: 8 AN: 150680 Hom.: 0 Cov.: 30 AF XY: 0.0000136 AC XY: 1 AN XY: 73492

African (AFR) AF: 0.00 AC: 0 AN: 41278

American (AMR) AF: 0.00 AC: 0 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000119 AC: 8 AN: 67422

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000718

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	0.094
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.50	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.25
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.026
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.11	T
Polyphen		0.036	B
Vest4		0.14
MVP		0.068
ClinPred		0.12	T
GERP RS		1.7
Varity_R		0.12
gMVP		0.074
Mutation Taster		=93/7	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: rs911115787; hg19: chr19-17434543;