rs12205331

Positions:

• chr6-34930678-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015245.3(ANKS1A):​c.198-36561C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,924 control chromosomes in the GnomAD database, including 1,970 homozygotes. 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: 𝑓 0.14 (1970 hom., cov: 31)
• Consequence: ANKS1A NM_015245.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS1A	NM_015245.3	c.198-36561C>T		intron_variant		ENST00000360359.5	NP_056060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKS1A	ENST00000360359.5	c.198-36561C>T		intron_variant		1	NM_015245.3	ENSP00000353518
ANKS1A	ENST00000649117.1	c.198-36561C>T		intron_variant				ENSP00000497393	P1
ANKS1A	ENST00000650178.1	c.198-36561C>T		intron_variant				ENSP00000497939

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20987 AN: 151806 Hom.: 1968 Cov.: 31

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0658

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.0982

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.138 AC: 20989 AN: 151924 Hom.: 1970 Cov.: 31 AF XY: 0.134 AC XY: 9968 AN XY: 74250

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.0658

Gnomad4 EAS AF: 0.0172

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.0976

Alfa AF: 0.177 Hom.: 3180

Bravo AF: 0.131

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs12205331; hg19: chr6-34898455;