NM_019046.3:c.1058A>G

Variant names:

• chr10-5878158-T-C
• rs1052420
• NM_019046.3:c.1058A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019046.3(ANKRD16):​c.1058A>G​(p.Gln353Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 1,613,964 control chromosomes in the GnomAD database, including 599,274 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.83 (52316 hom., cov: 33)
  • Exomes 𝑓: 0.86 (546958 hom.)
• Consequence: ANKRD16 NM_019046.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 34 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.275913E-7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019046.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD16	NM_019046.3	MANE Select	c.1058A>G	p.Gln353Arg	missense	Exon 7 of 8	NP_061919.1	Q6P6B7-1
	ANKRD16	NM_001009941.3		c.1058A>G	p.Gln353Arg	missense	Exon 7 of 7	NP_001009941.1	Q6P6B7-1
	ANKRD16	NM_001009943.3		c.*64A>G		3_prime_UTR	Exon 6 of 6	NP_001009943.1	Q6P6B7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD16	ENST00000380094.10	TSL:2 MANE Select	c.1058A>G	p.Gln353Arg	missense	Exon 7 of 8	ENSP00000369436.4	Q6P6B7-1
	ANKRD16	ENST00000380092.8	TSL:1	c.1058A>G	p.Gln353Arg	missense	Exon 7 of 7	ENSP00000369434.4	Q6P6B7-1
	ANKRD16	ENST00000958073.1		c.1232A>G	p.Gln411Arg	missense	Exon 8 of 8	ENSP00000628132.1

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125602 AN: 152068 Hom.: 52276 Cov.: 33

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.825

GnomAD2 exomes AF: 0.858 AC: 215702 AN: 251260 AF XY: 0.854

Gnomad AFR exome AF: 0.718

Gnomad AMR exome AF: 0.924

Gnomad ASJ exome AF: 0.818

Gnomad EAS exome AF: 0.859

Gnomad FIN exome AF: 0.885

Gnomad NFE exome AF: 0.877

Gnomad OTH exome AF: 0.859

GnomAD4 exome AF: 0.864 AC: 1263251 AN: 1461778 Hom.: 546958 Cov.: 56 AF XY: 0.862 AC XY: 626607 AN XY: 727188

African (AFR) AF: 0.706 AC: 23649 AN: 33480

American (AMR) AF: 0.917 AC: 41003 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 21408 AN: 26134

East Asian (EAS) AF: 0.859 AC: 34084 AN: 39696

South Asian (SAS) AF: 0.788 AC: 67962 AN: 86240

European-Finnish (FIN) AF: 0.885 AC: 47259 AN: 53410

Middle Eastern (MID) AF: 0.819 AC: 4724 AN: 5766

European-Non Finnish (NFE) AF: 0.874 AC: 971689 AN: 1111942

Other (OTH) AF: 0.852 AC: 51473 AN: 60390

GnomAD4 genome AF: 0.826 AC: 125700 AN: 152186 Hom.: 52316 Cov.: 33 AF XY: 0.826 AC XY: 61473 AN XY: 74394

African (AFR) AF: 0.717 AC: 29733 AN: 41472

American (AMR) AF: 0.874 AC: 13378 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2829 AN: 3472

East Asian (EAS) AF: 0.854 AC: 4422 AN: 5176

South Asian (SAS) AF: 0.786 AC: 3791 AN: 4824

European-Finnish (FIN) AF: 0.882 AC: 9353 AN: 10604

Middle Eastern (MID) AF: 0.774 AC: 226 AN: 292

European-Non Finnish (NFE) AF: 0.873 AC: 59387 AN: 68024

Other (OTH) AF: 0.826 AC: 1743 AN: 2110

Alfa AF: 0.859 Hom.: 261453

Bravo AF: 0.823

TwinsUK AF: 0.869 AC: 3221

ALSPAC AF: 0.873 AC: 3364

ESP6500AA AF: 0.715 AC: 3152

ESP6500EA AF: 0.876 AC: 7533

ExAC AF: 0.852 AC: 103481

Asia WGS AF: 0.842 AC: 2924 AN: 3478

EpiCase AF: 0.874

EpiControl AF: 0.873

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.34
DANN	Benign	0.97
DEOGEN2	Benign	0.00046	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.29	T
MetaRNN	Benign	9.3e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.059
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.051
Sift	Benign	0.38	T
Sift4G	Benign	0.48	T
Polyphen		0.0010	B
Vest4		0.036
MPC		0.20
ClinPred		0.0043	T
GERP RS		3.8
Varity_R		0.021
gMVP		0.45
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1052420; hg19: chr10-5920121; COSMIC: COSV107207027; COSMIC: COSV107207027;