12-100942466-C-T

Variant names:

• chr12-100942466-C-T
• rs1224091418
• NM_001286615.2:c.387C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001286615.2(ANO4):​c.387C>T​(p.Asn129Asn) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANO4 NM_001286615.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 0 publications found

Genes affected

ANO4 (HGNC:23837): (anoctamin 4) Enables intracellular calcium activated chloride channel activity. Involved in chloride transport. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ANO4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=1.3 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286615.2. 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
	ANO4	NM_001286615.2	MANE Select	c.387C>T	p.Asn129Asn	synonymous	Exon 5 of 28	NP_001273544.1	Q32M45-1
	ANO4	NM_001286616.1		c.387C>T	p.Asn129Asn	synonymous	Exon 4 of 27	NP_001273545.1	Q32M45-1
	ANO4	NM_178826.4		c.282C>T	p.Asn94Asn	synonymous	Exon 4 of 27	NP_849148.2	Q32M45-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO4	ENST00000392977.8	TSL:2 MANE Select	c.387C>T	p.Asn129Asn	synonymous	Exon 5 of 28	ENSP00000376703.3	Q32M45-1
	ANO4	ENST00000644049.1		c.885C>T	p.Asn295Asn	synonymous	Exon 7 of 30	ENSP00000494481.1	A0A2R8Y532
	ANO4	ENST00000852684.1		c.387C>T	p.Asn129Asn	synonymous	Exon 5 of 28	ENSP00000522743.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.3
DANN	Benign	0.67
PhyloP100		1.3

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: rs1224091418; hg19: chr12-101336244;