10-5887999-G-T

Variant names:

• chr10-5887999-G-T
• rs2296136
• NM_019046.3:c.383C>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.383C>A​(p.Ala128Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A128G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: ANKRD16 NM_019046.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.65

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, 0.912

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD16	NM_019046.3	c.383C>A	p.Ala128Asp	missense_variant	Exon 2 of 8	ENST00000380094.10	NP_061919.1
ANKRD16	NM_001009941.3	c.383C>A	p.Ala128Asp	missense_variant	Exon 2 of 7		NP_001009941.1
ANKRD16	NM_001009943.3	c.383C>A	p.Ala128Asp	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.383C>A	p.Ala128Asp	missense_variant	Exon 2 of 8	2	NM_019046.3	ENSP00000369436.4
ANKRD16	ENST00000380092.8	c.383C>A	p.Ala128Asp	missense_variant	Exon 2 of 7	1		ENSP00000369434.4
ANKRD16	ENST00000191063.8	c.383C>A	p.Ala128Asp	missense_variant	Exon 2 of 6	3		ENSP00000352361.6
ANKRD16	ENST00000492368.1	n.-29C>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000198 AC: 29 AN: 1461872 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 727236

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: 0.0000252

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T;T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Pathogenic	3.5	H;H;H
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.5	D;D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0050	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.93
MutPred		0.65		Gain of disorder (P = 0.034);Gain of disorder (P = 0.034);Gain of disorder (P = 0.034);
MVP		0.83
MPC		0.92
ClinPred		1.0	D
GERP RS		2.9
Varity_R		0.80
gMVP		0.86

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

LitVar

Other links and lift over

dbSNP: rs2296136; hg19: chr10-5929962;