19-17323659-T-A

Variant names:

• chr19-17323659-T-A
• rs1336423150
• NM_020959.3:c.3557A>T

Variant summary

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

The NM_020959.3(ANO8):​c.3557A>T​(p.Gln1186Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. Q1186P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: ANO8 NM_020959.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• Publications: 1 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10556403).

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.3557A>T	p.Gln1186Leu	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.3557A>T	p.Gln1186Leu	missense	Exon 18 of 18	ENSP00000159087.4	Q9HCE9-1
	ANO8	ENST00000597643.5	TSL:2	n.*2369A>T		non_coding_transcript_exon	Exon 18 of 18	ENSP00000469751.1	M0QYD2
	ANO8	ENST00000597643.5	TSL:2	n.*2369A>T		3_prime_UTR	Exon 18 of 18	ENSP00000469751.1	M0QYD2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000180 AC: 1 AN: 55676 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 25742

African (AFR) AF: 0.00 AC: 0 AN: 1140

American (AMR) AF: 0.00 AC: 0 AN: 88

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 346

East Asian (EAS) AF: 0.00 AC: 0 AN: 336

South Asian (SAS) AF: 0.00 AC: 0 AN: 1130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 84

European-Non Finnish (NFE) AF: 0.0000198 AC: 1 AN: 50466

Other (OTH) AF: 0.00 AC: 0 AN: 1810

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.31	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.34
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.0080
Sift	Uncertain	0.014	D
Sift4G	Benign	0.35	T
Polyphen		0.15	B
Vest4		0.15
MutPred		0.24		Gain of glycosylation at P1185 (P = 0.0559)
MVP		0.068
ClinPred		0.13	T
GERP RS		2.9
Varity_R		0.066
gMVP		0.15
Mutation Taster		=95/5	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: rs1336423150; hg19: chr19-17434468;