19-4207915-A-C

Position:

• chr19-4207915-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393985.1(ANKRD24):​c.779A>C​(p.Lys260Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,402,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ANKRD24 NM_001393985.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20185056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD24	NM_001393985.1	c.779A>C	p.Lys260Thr	missense_variant	10/22	ENST00000318934.9	NP_001380914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD24	ENST00000318934.9	c.779A>C	p.Lys260Thr	missense_variant	10/22	5	NM_001393985.1	ENSP00000321731.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1402704 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 692292

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: 9.22e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 06, 2024

The c.779A>C (p.K260T) alteration is located in exon 10 (coding exon 9) of the ANKRD24 gene. This alteration results from a A to C substitution at nucleotide position 779, causing the lysine (K) at amino acid position 260 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.0027	T;T;T;.
Eigen	Benign	-0.075
Eigen_PC	Benign	0.0045
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.72	.;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.1	.;N;.;N
REVEL	Benign	0.078
Sift	Benign	0.083	.;T;.;T
Sift4G	Benign	0.075	T;T;D;D
Polyphen		0.68	P;P;.;B
Vest4		0.41
MutPred		0.41		Loss of ubiquitination at K260 (P = 0.0183);Loss of ubiquitination at K260 (P = 0.0183);.;.;
MVP		0.66
MPC		0.78
ClinPred		0.59	D
GERP RS		3.8
Varity_R		0.069
gMVP		0.28

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-4207912;