18-23601263-C-A

Variant names:

• chr18-23601263-C-A
• rs368245092
• NM_173505.4:c.869G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173505.4(ANKRD29):​c.869G>T​(p.Arg290Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. R290H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD29 NM_173505.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17249247).

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.869G>T	p.Arg290Leu	missense	Exon 10 of 10	NP_775776.2	Q8N6D5-1
	ANKRD29	NM_001308238.2		c.770G>T	p.Arg257Leu	missense	Exon 9 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.869G>T	p.Arg290Leu	missense	Exon 10 of 10	ENSP00000468354.1	Q8N6D5-1
	ANKRD29	ENST00000965701.1		c.773G>T	p.Arg258Leu	missense	Exon 9 of 9	ENSP00000635760.1
	ANKRD29	ENST00000322980.13	TSL:2	c.770G>T	p.Arg257Leu	missense	Exon 9 of 9	ENSP00000323387.9	Q8N6D5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.054
PrimateAI	Benign	0.24	T
REVEL	Benign	0.090
Sift4G	Uncertain	0.051	T
Polyphen		0.59	P
Vest4		0.38
MutPred		0.40		Loss of MoRF binding (P = 0.0076)
MVP		0.61
MPC		0.34
ClinPred		0.96	D
GERP RS		1.6
Varity_R		0.11
gMVP		0.63
Mutation Taster		=86/14	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: rs368245092; hg19: chr18-21181227;