Genetic Variant ANKRD66:c.-39G>A (chr6-46749953-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001162435.3(ANKRD66):c.-39G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000309 in 1,519,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

ANKRD66
NM_001162435.3 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.707

Variant links:

Genes affected

ANKRD66 (HGNC:44669): (ankyrin repeat domain 66)

ANKRD66 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05796647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD66	NM_001162435.3 link	c.-39G>A		5_prime_UTR_variant	Exon 2 of 5	ENST00000565422.3	NP_001155907.3	B4E2M5
ANKRD66	XM_017010148.2 link	c.109G>A	p.Gly37Arg	missense_variant	Exon 2 of 5		XP_016865637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD66	ENST00000565422 link	c.-39G>A		5_prime_UTR_variant	Exon 2 of 5	2	NM_001162435.3	ENSP00000454770.2		B4E2M5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.0000330

AC:

AN:

151420

Hom.:

AF XY:

0.0000372

AC XY:

AN XY:

80548

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000440

Gnomad FIN exome

AF:

0.0000655

Gnomad NFE exome

AF:

0.0000349

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000314

AC:

AN:

1367606

Hom.:

Cov.:

AF XY:

0.0000355

AC XY:

AN XY:

676538

show subpopulations

Gnomad4 AFR exome

AF:

0.000130

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000382

Gnomad4 FIN exome

AF:

0.0000407

Gnomad4 NFE exome

AF:

0.0000305

Gnomad4 OTH exome

AF:

0.0000351

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000423

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.127G>A (p.G43R) alteration is located in exon 2 (coding exon 2) of the ANKRD66 gene. This alteration results from a G to A substitution at nucleotide position 127, causing the glycine (G) at amino acid position 43 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.2

DANN

Benign

0.71

DEOGEN2

Benign

0.0038

FATHMM_MKL

Benign

0.0091

LIST_S2

Benign

0.30

M_CAP

Benign

0.010

MetaRNN

Benign

0.058

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.24

Sift

Benign

0.51

Sift4G

Uncertain

0.050

Vest4

0.14

MVP

0.22

GERP RS

-2.3

Varity_R

0.033

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over