NM_015245.3:c.198-36561C>T

Variant names:

• chr6-34930678-C-T
• rs12205331
• NM_015245.3:c.198-36561C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 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.198-36561C>T		intron	N/A	NP_056060.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS1A	ENST00000360359.5	TSL:1 MANE Select	c.198-36561C>T		intron	N/A	ENSP00000353518.3
	ANKS1A	ENST00000649117.1		c.198-36561C>T		intron	N/A	ENSP00000497393.1
	ANKS1A	ENST00000650178.1		c.198-36561C>T		intron	N/A	ENSP00000497939.1

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

African (AFR) AF: 0.0371 AC: 1539 AN: 41434

American (AMR) AF: 0.165 AC: 2518 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0658 AC: 228 AN: 3466

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5170

South Asian (SAS) AF: 0.0742 AC: 357 AN: 4812

European-Finnish (FIN) AF: 0.198 AC: 2079 AN: 10522

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13831 AN: 67950

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

Alfa AF: 0.167 Hom.: 4897

Bravo AF: 0.131

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.60
PhyloP100		0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
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: rs12205331; hg19: chr6-34898455;