rs2005

Positions:

• chr6-35088666-A-G
• chr6-35088666-A-T

Variant summary

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

The NM_015245.3(ANKS1A):​c.*57A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 1,613,952 control chromosomes in the GnomAD database, including 650,376 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 0.89 (60946 hom., cov: 32)
  • Exomes 𝑓: 0.90 (589430 hom.)
• Consequence: ANKS1A NM_015245.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS1A	NM_015245.3	c.*57A>G		3_prime_UTR_variant	24/24	ENST00000360359.5	NP_056060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKS1A	ENST00000360359.5	c.*57A>G		3_prime_UTR_variant	24/24	1	NM_015245.3	ENSP00000353518

Frequencies

GnomAD3 genomes AF: 0.893 AC: 135935 AN: 152154 Hom.: 60900 Cov.: 32

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.906

GnomAD4 exome AF: 0.897 AC: 1310985 AN: 1461680 Hom.: 589430 Cov.: 63 AF XY: 0.895 AC XY: 650861 AN XY: 727176

Gnomad4 AFR exome AF: 0.889

Gnomad4 AMR exome AF: 0.915

Gnomad4 ASJ exome AF: 0.908

Gnomad4 EAS exome AF: 0.693

Gnomad4 SAS exome AF: 0.836

Gnomad4 FIN exome AF: 0.906

Gnomad4 NFE exome AF: 0.908

Gnomad4 OTH exome AF: 0.890

GnomAD4 genome AF: 0.893 AC: 136037 AN: 152272 Hom.: 60946 Cov.: 32 AF XY: 0.890 AC XY: 66248 AN XY: 74438

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.901

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.903

Gnomad4 NFE AF: 0.910

Gnomad4 OTH AF: 0.906

Alfa AF: 0.906 Hom.: 58209

Bravo AF: 0.894

Asia WGS AF: 0.793 AC: 2759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.041
DANN	Benign	0.36

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: rs2005; hg19: chr6-35056443;