10-5878141-C-A

Variant names:

• chr10-5878141-C-A
• rs772833678
• NM_019046.3:c.1075G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019046.3(ANKRD16):​c.1075G>T​(p.Ala359Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. A359T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ANKRD16 NM_019046.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06643137).

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.1075G>T	p.Ala359Ser	missense	Exon 7 of 8	NP_061919.1	Q6P6B7-1
	ANKRD16	NM_001009941.3		c.1075G>T	p.Ala359Ser	missense	Exon 7 of 7	NP_001009941.1	Q6P6B7-1
	ANKRD16	NM_001009943.3		c.*81G>T		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.1075G>T	p.Ala359Ser	missense	Exon 7 of 8	ENSP00000369436.4	Q6P6B7-1
	ANKRD16	ENST00000380092.8	TSL:1	c.1075G>T	p.Ala359Ser	missense	Exon 7 of 7	ENSP00000369434.4	Q6P6B7-1
	ANKRD16	ENST00000958073.1		c.1249G>T	p.Ala417Ser	missense	Exon 8 of 8	ENSP00000628132.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250708 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461444 Hom.: 0 Cov.: 29 AF XY: 0.00000550 AC XY: 4 AN XY: 727024

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111836

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.056
DANN	Benign	0.84
DEOGEN2	Benign	0.00068	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.2
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.050
Sift	Benign	0.27	T
Sift4G	Benign	0.14	T
Polyphen		0.0030	B
Vest4		0.075
MutPred		0.28		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.42
MPC		0.17
ClinPred		0.035	T
GERP RS		1.3
Varity_R		0.035
gMVP		0.24
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs772833678; hg19: chr10-5920104;