chr19-4199764-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/23 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

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD24	NM_001393985.1	c.118C>G	p.Arg40Gly	missense_variant	Exon 3 of 22	ENST00000318934.9	NP_001380914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD24	ENST00000318934.9	c.118C>G	p.Arg40Gly	missense_variant	Exon 3 of 22	5	NM_001393985.1	ENSP00000321731.4

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.30e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.3	.;N
REVEL	Benign	0.010
Sift	Benign	0.15	.;T
Sift4G	Benign	0.43	T;T
Polyphen		0.0050	B;B
Vest4		0.28
MutPred		0.34		Loss of MoRF binding (P = 0.0152);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs60004310; hg19: chr19-4199761;