18-23612148-T-A

Variant names:

• chr18-23612148-T-A
• rs1778380655
• NM_173505.4:c.766A>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.766A>T​(p.Ile256Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. I256V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANKRD29 NM_173505.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.655
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18713).

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.766A>T	p.Ile256Phe	missense	Exon 9 of 10	NP_775776.2	Q8N6D5-1
	ANKRD29	NM_001308238.2		c.723+5584A>T		intron	N/A	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.766A>T	p.Ile256Phe	missense	Exon 9 of 10	ENSP00000468354.1	Q8N6D5-1
	ANKRD29	ENST00000965701.1		c.670A>T	p.Ile224Phe	missense	Exon 8 of 9	ENSP00000635760.1
	ANKRD29	ENST00000863695.1		c.667A>T	p.Ile223Phe	missense	Exon 8 of 9	ENSP00000533754.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461750 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727160

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.66
PrimateAI	Benign	0.47	T
Sift4G	Benign	0.11	T
Polyphen		0.17	B
Vest4		0.40
MutPred		0.45		Loss of stability (P = 0.0298)
MVP		0.41
MPC		0.51
ClinPred		0.68	D
GERP RS		4.4
Varity_R		0.066
gMVP		0.43
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1778380655; hg19: chr18-21192112;