17-29607784-C-T

Position:

• chr17-29607784-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152345.5(ANKRD13B):​c.157C>T​(p.His53Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANKRD13B NM_152345.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.921

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD13B	NM_152345.5	c.157C>T	p.His53Tyr	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.157C>T	p.His53Tyr	missense_variant	2/15	2	NM_152345.5	ENSP00000378328.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450448 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721994

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

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

Sep 26, 2024

The c.157C>T (p.H53Y) 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 157, causing the histidine (H) at amino acid position 53 to be replaced by a tyrosine (Y). 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	0.90
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;.
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Uncertain	0.031	D
MutationAssessor	Benign	1.8	L;L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.6	.;D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.028	.;D
Sift4G	Uncertain	0.037	D;D
Polyphen		1.0	D;D
Vest4		0.95
MutPred		0.78		Loss of disorder (P = 0.0483);Loss of disorder (P = 0.0483);
MVP		0.91
MPC		2.1
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.44
gMVP		0.93

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: chr17-27934802;