18-23619625-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173505.4(ANKRD29):​c.533G>C​(p.Gly178Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,427,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G178V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ANKRD29 NM_173505.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41226757).

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>C	p.Gly178Ala	missense	Exon 7 of 10	NP_775776.2	Q8N6D5-1
	ANKRD29	NM_001308238.2		c.533G>C	p.Gly178Ala	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>C	p.Gly178Ala	missense	Exon 7 of 10	ENSP00000468354.1	Q8N6D5-1
	ANKRD29	ENST00000965701.1		c.533G>C	p.Gly178Ala	missense	Exon 7 of 9	ENSP00000635760.1
	ANKRD29	ENST00000322980.13	TSL:2	c.533G>C	p.Gly178Ala	missense	Exon 7 of 9	ENSP00000323387.9	Q8N6D5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000517 AC: 1 AN: 193328 AF XY: 0.00000922

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.01e-7 AC: 1 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: 0.00 AC: 0 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: 9.06e-7 AC: 1 AN: 1104314

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

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000170 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		4.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.023	D
Polyphen		0.27	B
Vest4		0.41
MutPred		0.78		Loss of catalytic residue at P174 (P = 0.0814)
MVP		0.54
MPC		0.51
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.57
gMVP		0.78
Mutation Taster		=81/19	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;