10-37130304-G-A

Variant names:

• chr10-37130304-G-A
• NM_052997.3:c.436G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_052997.3(ANKRD30A):​c.436G>A​(p.Ala146Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD30A NM_052997.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

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.436G>A	p.Ala146Thr	missense	Exon 3 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.436G>A	p.Ala146Thr	missense	Exon 3 of 36	ENSP00000354432.2	Q9BXX3
	ANKRD30A	ENST00000374660.7	TSL:5	c.436G>A	p.Ala146Thr	missense	Exon 3 of 42	ENSP00000363792.2	Q5W026
	ANKRD30A	ENST00000602533.7	TSL:5	c.436G>A	p.Ala146Thr	missense	Exon 3 of 36	ENSP00000473551.2	Q9BXX3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000207 AC: 3 AN: 1450940 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 721836

African (AFR) AF: 0.00 AC: 0 AN: 32536

American (AMR) AF: 0.00 AC: 0 AN: 42772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25944

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38668

South Asian (SAS) AF: 0.00 AC: 0 AN: 85066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107112

Other (OTH) AF: 0.00 AC: 0 AN: 59828

GnomAD4 genome Cov.: 33

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	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	-0.061
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0053	T
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		4.0
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.79		Gain of catalytic residue at H144 (P = 0.2062)
MVP		0.87
MPC		0.060
ClinPred		0.91	D
GERP RS		0.85
Varity_R		0.031
gMVP		0.51
Mutation Taster		=91/9	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

hg19: chr10-37419232;