10-5884052-C-T

Variant names:

• chr10-5884052-C-T
• NM_019046.3:c.604G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_019046.3(ANKRD16):​c.604G>A​(p.Asp202Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ANKRD16 NM_019046.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.35

Genes affected

ANKRD16 (HGNC:23471): (ankyrin repeat domain 16) Predicted to be involved in tRNA modification. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD16	NM_019046.3	c.604G>A	p.Asp202Asn	missense_variant	Exon 4 of 8	ENST00000380094.10	NP_061919.1
ANKRD16	NM_001009941.3	c.604G>A	p.Asp202Asn	missense_variant	Exon 4 of 7		NP_001009941.1
ANKRD16	NM_001009943.3	c.604G>A	p.Asp202Asn	missense_variant	Exon 4 of 6		NP_001009943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD16	ENST00000380094.10	c.604G>A	p.Asp202Asn	missense_variant	Exon 4 of 8	2	NM_019046.3	ENSP00000369436.4
ANKRD16	ENST00000380092.8	c.604G>A	p.Asp202Asn	missense_variant	Exon 4 of 7	1		ENSP00000369434.4
ANKRD16	ENST00000191063.8	c.604G>A	p.Asp202Asn	missense_variant	Exon 4 of 6	3		ENSP00000352361.6
ANKRD16	ENST00000492368.1	n.193G>A		non_coding_transcript_exon_variant	Exon 3 of 4	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461748 Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3 AN XY: 727174

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.604G>A (p.D202N) alteration is located in exon 4 (coding exon 4) of the ANKRD16 gene. This alteration results from a G to A substitution at nucleotide position 604, causing the aspartic acid (D) at amino acid position 202 to be replaced by an asparagine (N). 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	Pathogenic	0.76
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	.;D;D
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	1.6	L;L;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.78
MutPred		0.58		Loss of phosphorylation at Y200 (P = 0.1594);Loss of phosphorylation at Y200 (P = 0.1594);Loss of phosphorylation at Y200 (P = 0.1594);
MVP		0.87
MPC		0.69
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.76
gMVP		0.56

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: chr10-5926015;