10-37141817-C-T

Variant names:

• chr10-37141817-C-T
• rs547420743
• NM_052997.3:c.920C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052997.3(ANKRD30A):​c.920C>T​(p.Ala307Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A307E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANKRD30A NM_052997.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14930204).

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.920C>T	p.Ala307Val	missense	Exon 7 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.920C>T	p.Ala307Val	missense	Exon 7 of 36	ENSP00000354432.2	Q9BXX3
	ANKRD30A	ENST00000374660.7	TSL:5	c.920C>T	p.Ala307Val	missense	Exon 7 of 42	ENSP00000363792.2	Q5W026
	ANKRD30A	ENST00000602533.7	TSL:5	c.920C>T	p.Ala307Val	missense	Exon 7 of 36	ENSP00000473551.2	Q9BXX3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461348 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726994

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5554

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111800

Other (OTH) AF: 0.00 AC: 0 AN: 60356

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.33
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.059
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.11	T
Polyphen		0.98	D
Vest4		0.14
MutPred		0.32		Gain of relative solvent accessibility (P = 0.0999)
MVP		0.31
MPC		0.040
ClinPred		0.66	D
GERP RS		-1.1
Varity_R		0.051
gMVP		0.069
Mutation Taster		=100/0	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

dbSNP: rs547420743; hg19: chr10-37430745;