10-37132285-C-A

Variant names:

• chr10-37132285-C-A
• rs1836425203
• NM_052997.3:c.556C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052997.3(ANKRD30A):​c.556C>A​(p.Gln186Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ANKRD30A NM_052997.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.521
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10892731).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD30A	NM_052997.3	MANE Select	c.556C>A	p.Gln186Lys	missense	Exon 4 of 36	NP_443723.3	Q9BXX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD30A	ENST00000361713.2	TSL:5 MANE Select	c.556C>A	p.Gln186Lys	missense	Exon 4 of 36	ENSP00000354432.2	Q9BXX3
	ANKRD30A	ENST00000374660.7	TSL:5	c.556C>A	p.Gln186Lys	missense	Exon 4 of 42	ENSP00000363792.2	Q5W026
	ANKRD30A	ENST00000602533.7	TSL:5	c.556C>A	p.Gln186Lys	missense	Exon 4 of 36	ENSP00000473551.2	Q9BXX3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454276 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723012

African (AFR) AF: 0.00 AC: 0 AN: 33336

American (AMR) AF: 0.00 AC: 0 AN: 44028

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39444

South Asian (SAS) AF: 0.00 AC: 0 AN: 83938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108424

Other (OTH) AF: 0.0000166 AC: 1 AN: 60104

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.64
DANN	Benign	0.59
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.11	N
PhyloP100		-0.52
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.14
Sift	Benign	0.33	T
Sift4G	Benign	0.13	T
Polyphen		0.42	B
Vest4		0.18
MutPred		0.52		Gain of methylation at Q186 (P = 0.0662)
MVP		0.49
MPC		0.021
ClinPred		0.22	T
GERP RS		-4.7
Varity_R		0.11
gMVP		0.25
Mutation Taster		=96/4	polymorphism

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: rs1836425203; hg19: chr10-37421213;