rs1052420

Positions:

• chr10-5878158-T-A
• chr10-5878158-T-C
• chr10-5878158-T-G

Variant summary

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

The NM_019046.3(ANKRD16):​c.1058A>T​(p.Gln353Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign 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. Q353R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD16 NM_019046.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

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/exons	MANE	Protein	UniProt
ANKRD16	NM_019046.3	c.1058A>T	p.Gln353Leu	missense_variant	7/8	ENST00000380094.10	NP_061919.1
ANKRD16	NM_001009941.3	c.1058A>T	p.Gln353Leu	missense_variant	7/7		NP_001009941.1
ANKRD16	NM_001009943.3	c.*64A>T		3_prime_UTR_variant	6/6		NP_001009943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD16	ENST00000380094.10	c.1058A>T	p.Gln353Leu	missense_variant	7/8	2	NM_019046.3	ENSP00000369436	P1
ANKRD16	ENST00000380092.8	c.1058A>T	p.Gln353Leu	missense_variant	7/7	1		ENSP00000369434	P1
ANKRD16	ENST00000191063.8	c.*64A>T		3_prime_UTR_variant	6/6	3		ENSP00000352361

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461840 Hom.: 0 Cov.: 56 AF XY: 0.00 AC XY: 0 AN XY: 727224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	7.0
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0047	T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.34	.;T
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	0.072	P;P;P
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		0.22	B;B
Vest4		0.35
MutPred		0.42		Gain of loop (P = 0.002);Gain of loop (P = 0.002);
MVP		0.73
MPC		0.35
ClinPred		0.85	D
GERP RS		3.8
Varity_R		0.059
gMVP		0.51

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: rs1052420; hg19: chr10-5920121;