chr17-29609178-C-G

Position:

• chr17-29609178-C-G

Variant summary

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

The NM_152345.5(ANKRD13B):​c.658C>G​(p.Leu220Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD13B NM_152345.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.915

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD13B	NM_152345.5	c.658C>G	p.Leu220Val	missense_variant	6/15	ENST00000394859.8	NP_689558.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD13B	ENST00000394859.8	c.658C>G	p.Leu220Val	missense_variant	6/15	2	NM_152345.5	ENSP00000378328.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 23, 2023

The c.658C>G (p.L220V) alteration is located in exon 6 (coding exon 6) of the ANKRD13B gene. This alteration results from a C to G substitution at nucleotide position 658, causing the leucine (L) at amino acid position 220 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	0.15
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;.
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.7	.;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.013	.;D
Sift4G	Benign	0.074	T;T
Polyphen		0.93	P;P
Vest4		0.61
MutPred		0.40		Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);
MVP		0.75
MPC		1.8
ClinPred		0.86	D
GERP RS		4.8
Varity_R		0.21
gMVP		0.42

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: chr17-27936196;