6-34970052-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_015245.3(ANKS1A):c.321C>T(p.Asn107=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000422 in 1,614,134 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00058 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (1 hom.)
• Consequence: ANKS1A NM_015245.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.780

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 6-34970052-C-T is Benign according to our data. Variant chr6-34970052-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 721533.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.78 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS1A	NM_015245.3	c.321C>T	p.Asn107=	synonymous_variant	3/24	ENST00000360359.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS1A	ENST00000360359.5	c.321C>T	p.Asn107=	synonymous_variant	3/24	1	NM_015245.3
ANKS1A	ENST00000649117.1	c.321C>T	p.Asn107=	synonymous_variant	3/25			P1
ANKS1A	ENST00000650178.1	c.321C>T	p.Asn107=	synonymous_variant	3/10

Frequencies

GnomAD3 genomes AF: 0.000578 AC: 88 AN: 152186 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000354 AC: 89 AN: 251254 Hom.: 0 AF XY: 0.000346 AC XY: 47 AN XY: 135794

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000343

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000406 AC: 593 AN: 1461830 Hom.: 1 Cov.: 30 AF XY: 0.000385 AC XY: 280 AN XY: 727220

Gnomad4 AFR exome AF: 0.00114

Gnomad4 AMR exome AF: 0.000581

Gnomad4 ASJ exome AF: 0.00138

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000406

Gnomad4 OTH exome AF: 0.000563

GnomAD4 genome AF: 0.000578 AC: 88 AN: 152304 Hom.: 1 Cov.: 32 AF XY: 0.000497 AC XY: 37 AN XY: 74482

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000506 Hom.: 0

Bravo AF: 0.000672

EpiCase AF: 0.000654

EpiControl AF: 0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	1.5
Dann	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs150247971; hg19: chr6-34937829;