10-37130283-G-A

Variant names:

• chr10-37130283-G-A
• NM_052997.3:c.415G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052997.3(ANKRD30A):​c.415G>A​(p.Gly139Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,468 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANKRD30A NM_052997.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD30A	NM_052997.3	c.415G>A	p.Gly139Ser	missense_variant	Exon 3 of 36	ENST00000361713.2	NP_443723.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD30A	ENST00000361713.2	c.415G>A	p.Gly139Ser	missense_variant	Exon 3 of 36	5	NM_052997.3	ENSP00000354432.2
ANKRD30A	ENST00000374660.7	c.415G>A	p.Gly139Ser	missense_variant	Exon 3 of 42	5		ENSP00000363792.2
ANKRD30A	ENST00000602533.7	c.415G>A	p.Gly139Ser	missense_variant	Exon 3 of 36	5		ENSP00000473551.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453468 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 723196

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.247G>A (p.G83S) alteration is located in exon 3 (coding exon 3) of the ANKRD30A gene. This alteration results from a G to A substitution at nucleotide position 247, causing the glycine (G) at amino acid position 83 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T;T;.;.
Eigen	Benign	0.059
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.87	D;T;T;.
M_CAP	Benign	0.0055	T
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.5	M;.;.;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-4.9	.;D;D;.
REVEL	Benign	0.27
Sift	Benign	0.040	.;D;D;.
Sift4G	Uncertain	0.0080	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.30
MutPred		0.84		Loss of catalytic residue at G139 (P = 0.0297);.;.;.;
MVP		0.82
MPC		0.065
ClinPred		0.93	D
GERP RS		1.0
Varity_R		0.039
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-37419211;