16-4698025-C-T

Position:

• chr16-4698025-C-T

Variant summary

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

The NM_133450.4(ANKS3):​c.1762G>A​(p.Asp588Asn) 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. 13/21 in silico tools predict 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKS3 NM_133450.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.954

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 (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=0.0681164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS3	NM_133450.4	c.1762G>A	p.Asp588Asn	missense_variant	15/18	ENST00000304283.9	NP_597707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKS3	ENST00000304283.9	c.1762G>A	p.Asp588Asn	missense_variant	15/18	2	NM_133450.4	ENSP00000304586.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456950 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724488

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Dec 10, 2024

The c.1762G>A (p.D588N) alteration is located in exon 15 (coding exon 13) of the ANKS3 gene. This alteration results from a G to A substitution at nucleotide position 1762, causing the aspartic acid (D) at amino acid position 588 to be replaced by an asparagine (N). 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	0.091
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0049	T;T;T;T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.75	T;T;T;.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.068	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.;.;M;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.1	.;.;N;N;.
REVEL	Benign	0.036
Sift	Uncertain	0.0080	.;.;D;D;.
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		0.20	B;.;.;B;.
Vest4		0.12
MutPred		0.11		Gain of catalytic residue at D588 (P = 0.0533);.;.;Gain of catalytic residue at D588 (P = 0.0533);.;
MVP		0.26
MPC		0.022
ClinPred		0.11	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.063
gMVP		0.099

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: chr16-4748026;