chr19-17323734-C-T

Variant names:

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

Variant summary

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

The NM_020959.3(ANO8):​c.3482G>A​(p.Gly1161Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000949 in 1,054,084 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. G1161V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: ANO8 NM_020959.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.08961785).

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>A	p.Gly1161Asp	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>A	p.Gly1161Asp	missense	Exon 18 of 18	ENSP00000159087.4	Q9HCE9-1
	ANO8	ENST00000597643.5	TSL:2	n.*2294G>A		non_coding_transcript_exon	Exon 18 of 18	ENSP00000469751.1	M0QYD2
	ANO8	ENST00000597643.5	TSL:2	n.*2294G>A		3_prime_UTR	Exon 18 of 18	ENSP00000469751.1	M0QYD2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 9.49e-7 AC: 1 AN: 1054084 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 20100

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

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 902258

Other (OTH) AF: 0.00 AC: 0 AN: 41804

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.41	T
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.25
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.050
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.021	D
Polyphen		0.069	B
Vest4		0.14
MutPred		0.14		Gain of helix (P = 0.132)
MVP		0.18
ClinPred		0.12	T
GERP RS		1.7
Varity_R		0.17
gMVP		0.067
Mutation Taster		=92/8	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;