6-35088666-A-G

Variant names:

• chr6-35088666-A-G
• rs2005
• NM_015245.3:c.*57A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015245.3. 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
	ANKS1A	NM_015245.3	MANE Select	c.*57A>G		3_prime_UTR	Exon 24 of 24	NP_056060.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS1A	ENST00000360359.5	TSL:1 MANE Select	c.*57A>G		3_prime_UTR	Exon 24 of 24	ENSP00000353518.3
	ANKS1A	ENST00000649117.1		c.*1595A>G		3_prime_UTR	Exon 25 of 25	ENSP00000497393.1
	ANKS1A	ENST00000922348.1		c.*57A>G		3_prime_UTR	Exon 25 of 25	ENSP00000592407.1

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

African (AFR) AF: 0.889 AC: 29763 AN: 33478

American (AMR) AF: 0.915 AC: 40937 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 23741 AN: 26136

East Asian (EAS) AF: 0.693 AC: 27489 AN: 39694

South Asian (SAS) AF: 0.836 AC: 72119 AN: 86254

European-Finnish (FIN) AF: 0.906 AC: 48288 AN: 53278

Middle Eastern (MID) AF: 0.882 AC: 5082 AN: 5764

European-Non Finnish (NFE) AF: 0.908 AC: 1009825 AN: 1111976

Other (OTH) AF: 0.890 AC: 53741 AN: 60384

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

African (AFR) AF: 0.892 AC: 37090 AN: 41558

American (AMR) AF: 0.901 AC: 13791 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3168 AN: 3472

East Asian (EAS) AF: 0.656 AC: 3388 AN: 5162

South Asian (SAS) AF: 0.839 AC: 4044 AN: 4818

European-Finnish (FIN) AF: 0.903 AC: 9582 AN: 10612

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61928 AN: 68032

Other (OTH) AF: 0.906 AC: 1911 AN: 2110

Alfa AF: 0.905 Hom.: 85256

Bravo AF: 0.894

Asia WGS AF: 0.793 AC: 2759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.041
DANN	Benign	0.36
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2005; hg19: chr6-35056443; COSMIC: COSV107469438;