chr17-29607833-C-T

Position:

• chr17-29607833-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152345.5(ANKRD13B):​c.206C>T​(p.Ala69Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,452,686 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: 0.000012 (0 hom.)
• Consequence: ANKRD13B NM_152345.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08

Genes affected

ANKRD13B (HGNC:26363): (ankyrin repeat domain 13B) Enables ubiquitin-dependent protein binding activity. Involved in negative regulation of receptor internalization. Located in endosome; perinuclear region of cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD13B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2676525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD13B	NM_152345.5	c.206C>T	p.Ala69Val	missense_variant	2/15	ENST00000394859.8	NP_689558.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD13B	ENST00000394859.8	c.206C>T	p.Ala69Val	missense_variant	2/15	2	NM_152345.5	ENSP00000378328.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000117 AC: 17 AN: 1452686 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 722996

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: 0.0000153

Gnomad4 OTH exome AF: 0.00

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

May 16, 2024

The c.206C>T (p.A69V) alteration is located in exon 2 (coding exon 2) of the ANKRD13B gene. This alteration results from a C to T substitution at nucleotide position 206, causing the alanine (A) at amino acid position 69 to be replaced by a valine (V). 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	0.098
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T;T
Eigen	Benign	-0.043
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.96	D;.
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.8	.;N
REVEL	Benign	0.15
Sift	Benign	0.12	.;T
Sift4G	Benign	0.18	T;T
Polyphen		0.90	P;P
Vest4		0.36
MutPred		0.44		Gain of catalytic residue at A69 (P = 0.1359);Gain of catalytic residue at A69 (P = 0.1359);
MVP		0.73
MPC		1.4
ClinPred		0.91	D
GERP RS		2.6
Varity_R		0.065
gMVP		0.18

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: rs1188207609; hg19: chr17-27934851; COSMIC: COSV67473425; COSMIC: COSV67473425;