chr18-23619625-C-A

Variant names:

• chr18-23619625-C-A
• rs751042164
• NM_173505.4:c.533G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.917

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173505.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD29	NM_173505.4	MANE Select	c.533G>T	p.Gly178Val	missense	Exon 7 of 10	NP_775776.2	Q8N6D5-1
	ANKRD29	NM_001308238.2		c.533G>T	p.Gly178Val	missense	Exon 7 of 9	NP_001295167.1	Q8N6D5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD29	ENST00000592179.6	TSL:1 MANE Select	c.533G>T	p.Gly178Val	missense	Exon 7 of 10	ENSP00000468354.1	Q8N6D5-1
	ANKRD29	ENST00000965701.1		c.533G>T	p.Gly178Val	missense	Exon 7 of 9	ENSP00000635760.1
	ANKRD29	ENST00000322980.13	TSL:2	c.533G>T	p.Gly178Val	missense	Exon 7 of 9	ENSP00000323387.9	Q8N6D5-3

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

African (AFR) AF: 0.00 AC: 0 AN: 32432

American (AMR) AF: 0.00 AC: 0 AN: 40804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25298

East Asian (EAS) AF: 0.0000520 AC: 2 AN: 38470

South Asian (SAS) AF: 0.00 AC: 0 AN: 83620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5498

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104314

Other (OTH) AF: 0.00 AC: 0 AN: 59292

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.51	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		4.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.75
MutPred		0.80		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
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs751042164; hg19: chr18-21199589;