19-4199764-C-G

Variant names:

• chr19-4199764-C-G
• rs60004310
• NM_001393985.1:c.118C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001393985.1(ANKRD24):​c.118C>G​(p.Arg40Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 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. R40C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ANKRD24 NM_001393985.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05698195).

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.118C>G	p.Arg40Gly	missense	Exon 3 of 22	NP_001380914.1	Q8TF21-1
	ANKRD24	NM_001393552.1		c.118C>G	p.Arg40Gly	missense	Exon 3 of 23	NP_001380481.1
	ANKRD24	NM_001393553.1		c.118C>G	p.Arg40Gly	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.118C>G	p.Arg40Gly	missense	Exon 3 of 22	ENSP00000321731.4	Q8TF21-1
	ANKRD24	ENST00000597689.5	TSL:1	c.37-111C>G		intron	N/A	ENSP00000470227.1	M0QZ18
	ANKRD24	ENST00000966466.1		c.118C>G	p.Arg40Gly	missense	Exon 3 of 23	ENSP00000636525.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1384456 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 682596

African (AFR) AF: 0.00 AC: 0 AN: 31458

American (AMR) AF: 0.00 AC: 0 AN: 35232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24950

East Asian (EAS) AF: 0.00 AC: 0 AN: 35642

South Asian (SAS) AF: 0.00 AC: 0 AN: 78810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5104

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1075830

Other (OTH) AF: 0.00 AC: 0 AN: 57556

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.27
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.010
Sift	Benign	0.15	T
Sift4G	Benign	0.43	T
Polyphen		0.0050	B
Vest4		0.28
MutPred		0.34		Loss of MoRF binding (P = 0.0152)
MVP		0.099
MPC		0.33
ClinPred		0.054	T
GERP RS		0.82
Varity_R		0.079
gMVP		0.37
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.20		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs60004310; hg19: chr19-4199761;