13-110880092-C-T

Variant names:

• chr13-110880092-C-T
• rs755781873
• NM_017664.4:c.808G>A

Variant summary

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

The NM_017664.4(ANKRD10):​c.808G>A​(p.Val270Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,528 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: ANKRD10 NM_017664.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.170
• Publications: 3 publications found

Genes affected

ANKRD10 (HGNC:20265): (ankyrin repeat domain 10)

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=0.04234174).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017664.4. 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
	ANKRD10	NM_017664.4	MANE Select	c.808G>A	p.Val270Ile	missense	Exon 6 of 6	NP_060134.2	Q9NXR5-1
	ANKRD10	NR_104587.2		n.1005G>A		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD10	ENST00000267339.6	TSL:2 MANE Select	c.808G>A	p.Val270Ile	missense	Exon 6 of 6	ENSP00000267339.2	Q9NXR5-1
	ANKRD10	ENST00000886513.1		c.856G>A	p.Val286Ile	missense	Exon 7 of 7	ENSP00000556572.1
	ANKRD10	ENST00000956310.1		c.844G>A	p.Val282Ile	missense	Exon 6 of 6	ENSP00000626369.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000482 AC: 12 AN: 248858 AF XY: 0.0000519

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000448

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461528 Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20 AN XY: 726998

African (AFR) AF: 0.0000598 AC: 2 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

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

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111760

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Benign	0.83
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.17
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.034
Sift	Benign	0.43	T
Sift4G	Benign	0.43	T
Polyphen		0.11	B
Vest4		0.023
MutPred		0.34		Loss of loop (P = 0.0073)
MVP		0.41
MPC		0.34
ClinPred		0.030	T
GERP RS		1.6
Varity_R		0.012
gMVP		0.15
Mutation Taster		=96/4	polymorphism

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: rs755781873; hg19: chr13-111532439; COSMIC: COSV99941018; COSMIC: COSV99941018;