chr18-14748453-G-A

Position:

• chr18-14748453-G-A

Variant summary

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

The NM_001367607.2(ANKRD30B):​c.34G>A​(p.Val12Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,380,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000022 (0 hom.)
• Consequence: ANKRD30B NM_001367607.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.180

Genes affected

ANKRD30B (HGNC:24165): (ankyrin repeat domain 30B)

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=0.12089515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD30B	NM_001367607.2	c.34G>A	p.Val12Met	missense_variant	1/44	ENST00000690538.1	NP_001354536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD30B	ENST00000690538.1	c.34G>A	p.Val12Met	missense_variant	1/44		NM_001367607.2	ENSP00000510074	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1380988 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 679418

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: 0.00000187

Gnomad4 OTH exome AF: 0.0000176

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Sep 25, 2023

The c.34G>A (p.V12M) alteration is located in exon 1 (coding exon 1) of the ANKRD30B gene. This alteration results from a G to A substitution at nucleotide position 34, causing the valine (V) at amino acid position 12 to be replaced by a methionine (M). 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	0.37
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.3
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.0078	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.13
Sift	Benign	0.25	T
Sift4G	Benign	0.20	T
Vest4		0.14
MutPred		0.22		Gain of disorder (P = 0.0532);
MVP		0.17
MPC		0.038
ClinPred		0.17	T
GERP RS		0.14
Varity_R		0.053
gMVP		0.27

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: rs1265221333; hg19: chr18-14748452; COSMIC: COSV62811336;