chr19-4199711-C-T

Variant names:

• chr19-4199711-C-T
• rs1295715961
• NM_001393985.1:c.65C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001393985.1(ANKRD24):​c.65C>T​(p.Ser22Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000794 in 1,385,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: ANKRD24 NM_001393985.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3702097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD24	NM_001393985.1	c.65C>T	p.Ser22Phe	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.65C>T	p.Ser22Phe	missense_variant	Exon 3 of 22	5	NM_001393985.1	ENSP00000321731.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000794 AC: 11 AN: 1385686 Hom.: 0 Cov.: 30 AF XY: 0.00000732 AC XY: 5 AN XY: 683420

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: 0.0000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000929

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

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.65C>T (p.S22F) alteration is located in exon 3 (coding exon 2) of the ANKRD24 gene. This alteration results from a C to T substitution at nucleotide position 65, causing the serine (S) at amino acid position 22 to be replaced by a phenylalanine (F). 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0015	T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.62	.;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.0	.;N
REVEL	Benign	0.20
Sift	Uncertain	0.018	.;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.84	P;P
Vest4		0.56
MutPred		0.26		Gain of catalytic residue at S22 (P = 0.0013);Gain of catalytic residue at S22 (P = 0.0013);
MVP		0.33
MPC		0.83
ClinPred		0.74	D
GERP RS		3.3
Varity_R		0.13
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1295715961; hg19: chr19-4199708;