10-37141825-G-C

Position:

• chr10-37141825-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052997.3(ANKRD30A):​c.928G>C​(p.Val310Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ANKRD30A NM_052997.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.227

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]

ANKRD30A (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06441936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD30A	NM_052997.3	c.928G>C	p.Val310Leu	missense_variant	7/36	ENST00000361713.2	NP_443723.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD30A	ENST00000361713.2	c.928G>C	p.Val310Leu	missense_variant	7/36	5	NM_052997.3	ENSP00000354432.2
ANKRD30A	ENST00000374660.7	c.928G>C	p.Val310Leu	missense_variant	7/42	5		ENSP00000363792.2
ANKRD30A	ENST00000602533.7	c.928G>C	p.Val310Leu	missense_variant	7/36	5		ENSP00000473551.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

May 24, 2024

The c.760G>C (p.V254L) alteration is located in exon 7 (coding exon 7) of the ANKRD30A gene. This alteration results from a G to C substitution at nucleotide position 760, causing the valine (V) at amino acid position 254 to be replaced by a leucine (L). 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	0.19
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.1
DANN	Benign	0.90
DEOGEN2	Benign	0.00055	T;T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.35	T;T;T;.
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.064	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.0	L;.;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.28	.;N;N;.
REVEL	Benign	0.022
Sift	Benign	0.085	.;T;T;.
Sift4G	Benign	0.72	T;T;T;T
Polyphen		0.27	B;.;.;.
Vest4		0.14
MutPred		0.28		Loss of phosphorylation at T313 (P = 0.2278);.;.;.;
MVP		0.29
MPC		0.010
ClinPred		0.14	T
GERP RS		0.55
Varity_R		0.12
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-37430753;