chr18-23619625-C-A

Variant names:

• chr18-23619625-C-A
• NM_173505.4:c.533G>T

Variant summary

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

The NM_173505.4(ANKRD29):​c.533G>T​(p.Gly178Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,427,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANKRD29 NM_173505.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05

Genes affected

ANKRD29 (HGNC:27110): (ankyrin repeat domain 29) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.917

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD29	NM_173505.4	c.533G>T	p.Gly178Val	missense_variant	Exon 7 of 10	ENST00000592179.6	NP_775776.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD29	ENST00000592179.6	c.533G>T	p.Gly178Val	missense_variant	Exon 7 of 10	1	NM_173505.4	ENSP00000468354.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1427060 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 709542

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000520

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.533G>T (p.G178V) alteration is located in exon 7 (coding exon 7) of the ANKRD29 gene. This alteration results from a G to T substitution at nucleotide position 533, causing the glycine (G) at amino acid position 178 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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Uncertain	0.51	D
MutationAssessor	Pathogenic	4.1	H;H
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.4	.;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.99	D;P
Vest4		0.75
MutPred		0.80		Loss of disorder (P = 0.0577);Loss of disorder (P = 0.0577);
MVP		0.80
MPC		0.71
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.88
gMVP		0.88

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: chr18-21199589;