10-37141802-C-T

Variant names:

• chr10-37141802-C-T
• rs1837144594
• NM_052997.3:c.905C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052997.3(ANKRD30A):​c.905C>T​(p.Thr302Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ANKRD30A NM_052997.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.121

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12352717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD30A	NM_052997.3	c.905C>T	p.Thr302Ile	missense_variant	Exon 7 of 36	ENST00000361713.2	NP_443723.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD30A	ENST00000361713.2	c.905C>T	p.Thr302Ile	missense_variant	Exon 7 of 36	5	NM_052997.3	ENSP00000354432.2
ANKRD30A	ENST00000374660.7	c.905C>T	p.Thr302Ile	missense_variant	Exon 7 of 42	5		ENSP00000363792.2
ANKRD30A	ENST00000602533.7	c.905C>T	p.Thr302Ile	missense_variant	Exon 7 of 36	5		ENSP00000473551.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461106 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726896

Gnomad4 AFR exome AF: 0.0000299

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.737C>T (p.T246I) alteration is located in exon 7 (coding exon 7) of the ANKRD30A gene. This alteration results from a C to T substitution at nucleotide position 737, causing the threonine (T) at amino acid position 246 to be replaced by an isoleucine (I). 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	Benign	0.15
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.87
DEOGEN2	Benign	0.0036	T;T;.;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.36	T;T;T;.
M_CAP	Benign	0.00075	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.86	.;N;N;.
REVEL	Benign	0.059
Sift	Uncertain	0.013	.;D;D;.
Sift4G	Uncertain	0.0090	D;D;D;D
Polyphen		0.99	D;.;.;.
Vest4		0.16
MutPred		0.30		Loss of phosphorylation at T302 (P = 0.0096);.;.;.;
MVP		0.32
MPC		0.020
ClinPred		0.16	T
GERP RS		-1.1
Varity_R		0.065
gMVP		0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs1837144594; hg19: chr10-37430730;