18-14748633-A-G

Position:

• chr18-14748633-A-G

Variant summary

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

The NM_001367607.2(ANKRD30B):​c.214A>G​(p.Lys72Glu) 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: ANKRD30B NM_001367607.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.154

Genes affected

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

ANKRD30B (HGNC:):

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=0.1026724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD30B	NM_001367607.2	c.214A>G	p.Lys72Glu	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.214A>G	p.Lys72Glu	missense_variant	1/44		NM_001367607.2	ENSP00000510074.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jan 27, 2022

The c.214A>G (p.K72E) alteration is located in exon 1 (coding exon 1) of the ANKRD30B gene. This alteration results from a A to G substitution at nucleotide position 214, causing the lysine (K) at amino acid position 72 to be replaced by a glutamic acid (E). 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	Pathogenic	0.71
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.8
DANN	Benign	0.64
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.033	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.44	N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.091
Sift	Benign	0.23	T
Sift4G	Benign	1.0	T
Vest4		0.17
MutPred		0.50		Loss of MoRF binding (P = 0.0116);
MVP		0.18
MPC		0.038
ClinPred		0.15	T
GERP RS		0.92
Varity_R		0.087
gMVP		0.15

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: chr18-14748632;