NM_001393985.1:c.101C>A

Variant names:

• chr19-4199747-C-A
• rs1475684729
• NM_001393985.1:c.101C>A

Variant summary

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

The NM_001393985.1(ANKRD24):​c.101C>A​(p.Pro34Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,385,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P34S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANKRD24 NM_001393985.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 0 publications found

Genes affected

ANKRD24 (HGNC:29424): (ankyrin repeat domain 24)

ANKRD24 Gene-Disease associations (from GenCC):

• sensorineural hearing loss disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000306086 (HGNC:):

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=0.20177227).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393985.1. 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
	ANKRD24	NM_001393985.1	MANE Select	c.101C>A	p.Pro34Gln	missense	Exon 3 of 22	NP_001380914.1	Q8TF21-1
	ANKRD24	NM_001393552.1		c.101C>A	p.Pro34Gln	missense	Exon 3 of 23	NP_001380481.1
	ANKRD24	NM_001393553.1		c.101C>A	p.Pro34Gln	missense	Exon 3 of 22	NP_001380482.1	Q8TF21-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD24	ENST00000318934.9	TSL:5 MANE Select	c.101C>A	p.Pro34Gln	missense	Exon 3 of 22	ENSP00000321731.4	Q8TF21-1
	ANKRD24	ENST00000597689.5	TSL:1	c.37-128C>A		intron	N/A	ENSP00000470227.1	M0QZ18
	ANKRD24	ENST00000966466.1		c.101C>A	p.Pro34Gln	missense	Exon 3 of 23	ENSP00000636525.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1385672 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 683266

African (AFR) AF: 0.00 AC: 0 AN: 31466

American (AMR) AF: 0.00 AC: 0 AN: 35396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25066

East Asian (EAS) AF: 0.00 AC: 0 AN: 35646

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4882

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076498

Other (OTH) AF: 0.00 AC: 0 AN: 57586

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.095
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.45
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.096
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.050	T
Polyphen		1.0	D
Vest4		0.33
MutPred		0.29		Loss of catalytic residue at P34 (P = 0.025)
MVP		0.48
MPC		0.35
ClinPred		0.56	D
GERP RS		3.3
Varity_R		0.13
gMVP		0.28
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1475684729; hg19: chr19-4199744;