chr10-37219650-CTG-C

Variant names:

• chr10-37219650-CTG-C
• rs763931520
• NM_052997.3:c.3939_3940delTG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_052997.3(ANKRD30A):​c.3939_3940delTG​(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 (★). 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 criteria provided, single submitter U:2
• Conservation: PhyloP100: 2.06
• Publications: 5 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052997.3. 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
	ANKRD30A	NM_052997.3	MANE Select	c.3939_3940delTG	p.Glu1314ThrfsTer28	frameshift	Exon 34 of 36	NP_443723.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD30A	ENST00000361713.2	TSL:5 MANE Select	c.3939_3940delTG	p.Glu1314ThrfsTer28	frameshift	Exon 34 of 36	ENSP00000354432.2
	ANKRD30A	ENST00000374660.7	TSL:5	c.4296_4297delTG	p.Glu1433ThrfsTer28	frameshift	Exon 40 of 42	ENSP00000363792.2
	ANKRD30A	ENST00000602533.7	TSL:5	c.3939_3940delTG	p.Glu1314ThrfsTer28	frameshift	Exon 34 of 36	ENSP00000473551.2

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

GnomAD2 exomes AF: 0.00264 AC: 653 AN: 247458 AF XY: 0.00270

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 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

African (AFR) AF: 0.000691 AC: 23 AN: 33302

American (AMR) AF: 0.000719 AC: 32 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86114

European-Finnish (FIN) AF: 0.00405 AC: 216 AN: 53348

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5742

European-Non Finnish (NFE) AF: 0.00524 AC: 5818 AN: 1110154

Other (OTH) AF: 0.00583 AC: 351 AN: 60188

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

African (AFR) AF: 0.000849 AC: 35 AN: 41228

American (AMR) AF: 0.000997 AC: 15 AN: 15048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00604 AC: 64 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00466 AC: 314 AN: 67340

Other (OTH) AF: 0.00 AC: 0 AN: 2068

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:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

Familial cancer of breast Uncertain:1

Feb 01, 2014

Faculty of Pharmacy, Medical University of Gdansk

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=189/11	disease causing (fs/PTC)

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: rs763931520; hg19: chr10-37508578;