rs763931520

Positions:

• chr10-37219650-CTG-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_052997.3(ANKRD30A):​c.3939_3940del​(p.Glu1314ThrfsTer28) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00429 in 1,609,780 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 30)
  • Exomes 𝑓: 0.0044 (23 hom.)
• Consequence: ANKRD30A NM_052997.3 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.06

Genes affected

ANKRD30A (HGNC:17234): (ankyrin repeat domain 30A) This gene encodes a DNA-binding transcription factor that is uniquely expressed in mammary epithelium and the testis. Altered expression levels have been associated with breast cancer progression. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD30A	NM_052997.3	c.3939_3940del	p.Glu1314ThrfsTer28	frameshift_variant	34/36	ENST00000361713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD30A	ENST00000361713.2	c.3939_3940del	p.Glu1314ThrfsTer28	frameshift_variant	34/36	5	NM_052997.3	A2
ANKRD30A	ENST00000374660.7	c.4296_4297del	p.Glu1433ThrfsTer28	frameshift_variant	40/42	5		P4
ANKRD30A	ENST00000602533.7	c.3939_3940del	p.Glu1314ThrfsTer28	frameshift_variant	34/36	5		A2
ANKRD30A	ENST00000696674.1	c.672_673del	p.Glu225ThrfsTer28	frameshift_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.00304 AC: 459 AN: 150902 Hom.: 2 Cov.: 30

Gnomad AFR AF: 0.000849

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.000997

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00604

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00466

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00264 AC: 653 AN: 247458 Hom.: 2 AF XY: 0.00270 AC XY: 362 AN XY: 134322

Gnomad AFR exome AF: 0.000587

Gnomad AMR exome AF: 0.000671

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00377

Gnomad NFE exome AF: 0.00470

Gnomad OTH exome AF: 0.00217

GnomAD4 exome AF: 0.00442 AC: 6444 AN: 1458878 Hom.: 23 AF XY: 0.00421 AC XY: 3058 AN XY: 725754

Gnomad4 AFR exome AF: 0.000691

Gnomad4 AMR exome AF: 0.000719

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00405

Gnomad4 NFE exome AF: 0.00524

Gnomad4 OTH exome AF: 0.00583

GnomAD4 genome AF: 0.00304 AC: 459 AN: 150902 Hom.: 2 Cov.: 30 AF XY: 0.00305 AC XY: 225 AN XY: 73678

Gnomad4 AFR AF: 0.000849

Gnomad4 AMR AF: 0.000997

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00604

Gnomad4 NFE AF: 0.00466

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00261 Hom.: 0

Bravo AF: 0.00261

EpiCase AF: 0.00415

EpiControl AF: 0.00392

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial cancer of breast Uncertain:1

Uncertain significance, no assertion criteria provided

research

Faculty of Pharmacy, Medical University of Gdansk

Feb 01, 2014

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Computational scores

Source: dbNSFP v4.3

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: rs763931520; hg19: chr10-37508578;