16-4730261-G-C

Variant names:

• chr16-4730261-G-C
• rs859302
• NM_133450.4:c.-2-110C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133450.4(ANKS3):​c.-2-110C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000315 in 952,548 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: ANKS3 NM_133450.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.870
• Publications: 7 publications found

Genes affected

ANKS3 (HGNC:29422): (ankyrin repeat and sterile alpha motif domain containing 3) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ANKS3 Gene-Disease associations (from GenCC):

• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• laterality defects, autosomal dominant

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000266994 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133450.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS3	NM_133450.4	MANE Select	c.-2-110C>G		intron	N/A	NP_597707.1
	ANKS3	NM_001242929.2		c.-2-110C>G		intron	N/A	NP_001229858.1
	ANKS3	NM_001308089.2		c.-190-110C>G		intron	N/A	NP_001295018.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS3	ENST00000304283.9	TSL:2 MANE Select	c.-2-110C>G		intron	N/A	ENSP00000304586.4
	ANKS3	ENST00000592077.5	TSL:1	n.-2-110C>G		intron	N/A	ENSP00000465203.1
	ANKS3	ENST00000585773.5	TSL:2	c.-49-3084C>G		intron	N/A	ENSP00000465294.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000315 AC: 3 AN: 952548 Hom.: 0 Cov.: 12 AF XY: 0.00000216 AC XY: 1 AN XY: 463092

African (AFR) AF: 0.00 AC: 0 AN: 20348

American (AMR) AF: 0.00 AC: 0 AN: 10886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14566

East Asian (EAS) AF: 0.00 AC: 0 AN: 27250

South Asian (SAS) AF: 0.00 AC: 0 AN: 33910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28182

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

European-Non Finnish (NFE) AF: 0.00000388 AC: 3 AN: 774004

Other (OTH) AF: 0.00 AC: 0 AN: 40610

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.53
DANN	Benign	0.70
PhyloP100		-0.87
PromoterAI		-0.0060	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs859302; hg19: chr16-4780262;