6-34994416-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_015245.3(ANKS1A):c.1417A>G(p.Thr473Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000913 in 1,611,988 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (4 hom.)
• Consequence: ANKS1A NM_015245.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00600

Genes affected

ANKS1A (HGNC:20961): (ankyrin repeat and sterile alpha motif domain containing 1A) Predicted to enable ephrin receptor binding activity. Predicted to be involved in ephrin receptor signaling pathway; neuron remodeling; and substrate-dependent cell migration. Predicted to act upstream of or within negative regulation of ubiquitin-dependent protein catabolic process and regulation of ephrin receptor signaling pathway. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, ANKS1A
• BP4: Computational evidence support a benign effect (MetaRNN=0.0038804114).
• BP6: Variant 6-34994416-A-G is Benign according to our data. Variant chr6-34994416-A-G is described in ClinVar as [Benign]. Clinvar id is 768082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS1A	NM_015245.3	c.1417A>G	p.Thr473Ala	missense_variant	10/24	ENST00000360359.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS1A	ENST00000360359.5	c.1417A>G	p.Thr473Ala	missense_variant	10/24	1	NM_015245.3
ANKS1A	ENST00000649117.1	c.1480A>G	p.Thr494Ala	missense_variant	11/25			P1

Frequencies

GnomAD3 genomes AF: 0.00451 AC: 687 AN: 152230 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00121 AC: 305 AN: 251300 Hom.: 2 AF XY: 0.000965 AC XY: 131 AN XY: 135812

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000535 AC: 781 AN: 1459640 Hom.: 4 Cov.: 33 AF XY: 0.000485 AC XY: 352 AN XY: 726176

Gnomad4 AFR exome AF: 0.0131

Gnomad4 AMR exome AF: 0.00204

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000115

Gnomad4 OTH exome AF: 0.00178

GnomAD4 genome AF: 0.00453 AC: 690 AN: 152348 Hom.: 5 Cov.: 32 AF XY: 0.00424 AC XY: 316 AN XY: 74506

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00108 Hom.: 2

Bravo AF: 0.00571

ESP6500AA AF: 0.0141 AC: 62

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00139 AC: 169

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	5.4
Dann	Benign	0.97
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.52	T;T
MetaRNN	Benign	0.0039	T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
Polyphen		0.0020	.;B
Vest4		0.17
MVP		0.26
MPC		0.32
ClinPred		0.0043	T
GERP RS		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.090

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

LitVar

Other links and lift over

dbSNP: rs78397895; hg19: chr6-34962193;