18-14764078-G-A

Position:

• chr18-14764078-G-A

Variant summary

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

The NM_001367607.2(ANKRD30B):​c.1213G>A​(p.Ala405Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,373,040 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: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ANKRD30B NM_001367607.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0770

Genes affected

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

LOC105372008 (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=0.06784764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD30B	NM_001367607.2	c.1213G>A	p.Ala405Thr	missense_variant	7/44	ENST00000690538.1	NP_001354536.1
LOC105372008	XR_935181.3	n.116-1546C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD30B	ENST00000690538.1	c.1213G>A	p.Ala405Thr	missense_variant	7/44		NM_001367607.2	ENSP00000510074	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1373040 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 676752

Gnomad4 AFR exome AF: 0.0000339

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: 9.30e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Aug 08, 2022

The c.1213G>A (p.A405T) alteration is located in exon 7 (coding exon 7) of the ANKRD30B gene. This alteration results from a G to A substitution at nucleotide position 1213, causing the alanine (A) at amino acid position 405 to be replaced by a threonine (T). 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	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.81	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.035
Sift	Benign	0.99	T
Sift4G	Benign	0.12	T
Vest4		0.029
MutPred		0.36		Gain of glycosylation at A405 (P = 0.0266);
MVP		0.27
MPC		0.10
ClinPred		0.56	D
GERP RS		0.23
Varity_R		0.043
gMVP		0.021

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: rs1306988857; hg19: chr18-14764077; COSMIC: COSV62815360; COSMIC: COSV62815360;