10-37129970-A-G

Position:

• chr10-37129970-A-G

Variant summary

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

The NM_052997.3(ANKRD30A):​c.299A>G​(p.Asp100Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD30A NM_052997.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.31

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/exons	MANE	Protein	UniProt
ANKRD30A	NM_052997.3	c.299A>G	p.Asp100Gly	missense_variant	2/36	ENST00000361713.2	NP_443723.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD30A	ENST00000361713.2	c.299A>G	p.Asp100Gly	missense_variant	2/36	5	NM_052997.3	ENSP00000354432	A2
ANKRD30A	ENST00000374660.7	c.299A>G	p.Asp100Gly	missense_variant	2/42	5		ENSP00000363792	P4
ANKRD30A	ENST00000602533.7	c.299A>G	p.Asp100Gly	missense_variant	2/36	5		ENSP00000473551	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1427360 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 709688

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.131A>G (p.D44G) alteration is located in exon 2 (coding exon 2) of the ANKRD30A gene. This alteration results from a A to G substitution at nucleotide position 131, causing the aspartic acid (D) at amino acid position 44 to be replaced by a glycine (G). 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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;T;.;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.28	T;T;T;.
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.9	L;.;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.2	.;D;D;.
REVEL	Benign	0.24
Sift	Uncertain	0.0050	.;D;D;.
Sift4G	Uncertain	0.019	D;D;D;D
Polyphen		0.39	B;.;.;.
Vest4		0.40
MutPred		0.74		Loss of stability (P = 0.0364);.;.;.;
MVP		0.75
MPC		0.046
ClinPred		0.95	D
GERP RS		2.0
Varity_R		0.083
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr10-37418898;