6-35072643-T-C

Variant names:

• chr6-35072643-T-C
• rs820065
• NM_015245.3:c.2185-5915T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015245.3(ANKS1A):​c.2185-5915T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,168 control chromosomes in the GnomAD database, including 49,711 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 0.80 (49711 hom., cov: 33)
• Consequence: ANKS1A NM_015245.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.895 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS1A	NM_015245.3	MANE Select	c.2185-5915T>C		intron	N/A	NP_056060.2	Q92625-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS1A	ENST00000360359.5	TSL:1 MANE Select	c.2185-5915T>C		intron	N/A	ENSP00000353518.3	Q92625-1
	ANKS1A	ENST00000649117.1		c.2248-5915T>C		intron	N/A	ENSP00000497393.1	A0A3B3ISP1
	ANKS1A	ENST00000922348.1		c.2185-5915T>C		intron	N/A	ENSP00000592407.1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121694 AN: 152050 Hom.: 49679 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.800 AC: 121779 AN: 152168 Hom.: 49711 Cov.: 33 AF XY: 0.807 AC XY: 60044 AN XY: 74400

African (AFR) AF: 0.639 AC: 26520 AN: 41482

American (AMR) AF: 0.846 AC: 12943 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2399 AN: 3468

East Asian (EAS) AF: 0.896 AC: 4620 AN: 5158

South Asian (SAS) AF: 0.918 AC: 4422 AN: 4818

European-Finnish (FIN) AF: 0.938 AC: 9964 AN: 10620

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.856 AC: 58183 AN: 68004

Other (OTH) AF: 0.783 AC: 1648 AN: 2106

Alfa AF: 0.834 Hom.: 144586

Bravo AF: 0.783

Asia WGS AF: 0.891 AC: 3095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.34
PhyloP100		-0.37
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: rs820065; hg19: chr6-35040420;