10-5887890-C-G

Variant names:

• chr10-5887890-C-G
• rs761953271
• NM_019046.3:c.492G>C

Variant summary

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

The NM_019046.3(ANKRD16):​c.492G>C​(p.Trp164Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ANKRD16 NM_019046.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD16	NM_019046.3	c.492G>C	p.Trp164Cys	missense_variant	Exon 2 of 8	ENST00000380094.10	NP_061919.1
ANKRD16	NM_001009941.3	c.492G>C	p.Trp164Cys	missense_variant	Exon 2 of 7		NP_001009941.1
ANKRD16	NM_001009943.3	c.492G>C	p.Trp164Cys	missense_variant	Exon 2 of 6		NP_001009943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD16	ENST00000380094.10	c.492G>C	p.Trp164Cys	missense_variant	Exon 2 of 8	2	NM_019046.3	ENSP00000369436.4
ANKRD16	ENST00000380092.8	c.492G>C	p.Trp164Cys	missense_variant	Exon 2 of 7	1		ENSP00000369434.4
ANKRD16	ENST00000191063.8	c.492G>C	p.Trp164Cys	missense_variant	Exon 2 of 6	3		ENSP00000352361.6
ANKRD16	ENST00000492368.1	n.81G>C		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000279 AC: 7 AN: 251326 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135860

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461818 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727212

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: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.492G>C (p.W164C) alteration is located in exon 2 (coding exon 2) of the ANKRD16 gene. This alteration results from a G to C substitution at nucleotide position 492, causing the tryptophan (W) at amino acid position 164 to be replaced by a cysteine (C). 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	0.86
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.017	T;T;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.10	N;N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-6.9	D;D;D
REVEL	Uncertain	0.42
Sift	Benign	0.19	T;T;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.24	B;B;.
Vest4		0.59
MutPred		0.51		Gain of methylation at K165 (P = 0.0193);Gain of methylation at K165 (P = 0.0193);Gain of methylation at K165 (P = 0.0193);
MVP		0.65
MPC		0.34
ClinPred		0.23	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.72
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs761953271; hg19: chr10-5929853;