chr19-4200004-G-T

Position:

• chr19-4200004-G-T

Variant summary

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

The NM_001393985.1(ANKRD24):​c.253G>T​(p.Ala85Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000708 in 1,411,556 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ANKRD24 NM_001393985.1 missense, splice_region
• Scores: Splicing: ADA: 0.5315
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.61

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD24	NM_001393985.1	c.253G>T	p.Ala85Ser	missense_variant, splice_region_variant	4/22	ENST00000318934.9	NP_001380914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD24	ENST00000318934.9	c.253G>T	p.Ala85Ser	missense_variant, splice_region_variant	4/22	5	NM_001393985.1	ENSP00000321731.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1411556 Hom.: 0 Cov.: 70 AF XY: 0.00000144 AC XY: 1 AN XY: 696842

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.: 33

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

Oct 01, 2024

The c.253G>T (p.A85S) alteration is located in exon 4 (coding exon 3) of the ANKRD24 gene. This alteration results from a G to T substitution at nucleotide position 253, causing the alanine (A) at amino acid position 85 to be replaced by a serine (S). 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	0.29
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.87	.;D;D;D
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.4	L;L;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.3	.;N;.;N
REVEL	Uncertain	0.46
Sift	Benign	0.051	.;T;.;D
Sift4G	Uncertain	0.048	D;D;T;T
Polyphen		0.92	P;P;.;P
Vest4		0.72
MutPred		0.73		Gain of disorder (P = 0.0409);Gain of disorder (P = 0.0409);.;.;
MVP		0.61
MPC		0.62
ClinPred		0.92	D
GERP RS		2.9
Varity_R		0.091
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.53
dbscSNV1_RF	Benign	0.53
SpliceAI score (max)		0.11		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: chr19-4200001;