19-17323596-T-C

Position:

• chr19-17323596-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020959.3(ANO8):​c.3620A>G​(p.Asp1207Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 27)
• Consequence: ANO8 NM_020959.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.04

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]

ANO8 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0708594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO8	NM_020959.3	c.3620A>G	p.Asp1207Gly	missense_variant	18/18	ENST00000159087.7	NP_066010.1
ANO8	XR_936199.4	n.4469A>G		non_coding_transcript_exon_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO8	ENST00000159087.7	c.3620A>G	p.Asp1207Gly	missense_variant	18/18	1	NM_020959.3	ENSP00000159087.4
ANO8	ENST00000597643.5	n.*2432A>G		non_coding_transcript_exon_variant	18/18	2		ENSP00000469751.1
ANO8	ENST00000597643.5	n.*2432A>G		3_prime_UTR_variant	18/18	2		ENSP00000469751.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2022

The c.3620A>G (p.D1207G) alteration is located in exon 18 (coding exon 18) of the ANO8 gene. This alteration results from a A to G substitution at nucleotide position 3620, causing the aspartic acid (D) at amino acid position 1207 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.8
DANN	Benign	0.91
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.35	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.064
Sift	Benign	0.066	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.038
MutPred		0.15		Gain of glycosylation at P1208 (P = 0.149);
MVP		0.093
ClinPred		0.20	T
GERP RS		-2.7
Varity_R		0.076
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17434405;