19-17323596-T-C

Variant names:

• chr19-17323596-T-C
• NM_020959.3:c.3620A>G

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.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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1207N) has been classified 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
• 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=0.0708594).

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.3620A>G	p.Asp1207Gly	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.3620A>G	p.Asp1207Gly	missense	Exon 18 of 18	ENSP00000159087.4	Q9HCE9-1
	ANO8	ENST00000597643.5	TSL:2	n.*2432A>G		non_coding_transcript_exon	Exon 18 of 18	ENSP00000469751.1	M0QYD2
	ANO8	ENST00000597643.5	TSL:2	n.*2432A>G		3_prime_UTR	Exon 18 of 18	ENSP00000469751.1	M0QYD2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 27

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	0.089
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
PhyloP100		-1.0
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
Mutation Taster		=97/3	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

hg19: chr19-17434405;