chr17-29611579-G-T

Position:

• chr17-29611579-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152345.5(ANKRD13B):​c.905G>T​(p.Gly302Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD13B NM_152345.5 missense, splice_region
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.62

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.754

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD13B	NM_152345.5	c.905G>T	p.Gly302Val	missense_variant, splice_region_variant	9/15	ENST00000394859.8	NP_689558.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD13B	ENST00000394859.8	c.905G>T	p.Gly302Val	missense_variant, splice_region_variant	9/15	2	NM_152345.5	ENSP00000378328.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Mar 20, 2024

The c.905G>T (p.G302V) alteration is located in exon 9 (coding exon 9) of the ANKRD13B gene. This alteration results from a G to T substitution at nucleotide position 905, causing the glycine (G) at amino acid position 302 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	0.28
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.91	D;.
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-4.8	.;D
REVEL	Uncertain	0.39
Sift	Benign	0.077	.;T
Sift4G	Benign	0.084	T;T
Polyphen		0.62	P;P
Vest4		0.85
MutPred		0.36		Loss of disorder (P = 0.0337);Loss of disorder (P = 0.0337);
MVP		0.86
MPC		2.2
ClinPred		0.97	D
GERP RS		6.0
Varity_R		0.65
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.99
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.42		Position offset: 0

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: chr17-27938597;