Variant 3-149761497-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001144960.3(ANKUB1):c.1622A>G(p.Glu541Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,551,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 0 hom. )

Consequence

ANKUB1
NM_001144960.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.870

Variant links:

Genes affected

ANKUB1 (HGNC:29642): (ankyrin repeat and ubiquitin domain containing 1)

ANKUB1 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=0.008916736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKUB1	NM_001144960.3 linkuse as main transcript	c.1622A>G	p.Glu541Gly	missense_variant	6/6	ENST00000446160.7	NP_001138432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKUB1	ENST00000446160.7 linkuse as main transcript	c.1622A>G	p.Glu541Gly	missense_variant	6/6	5	NM_001144960.3	ENSP00000387907	P1	A6NFN9-3
ANKUB1	ENST00000484019.1 linkuse as main transcript	c.*1392A>G		3_prime_UTR_variant, NMD_transcript_variant	6/6	1		ENSP00000420428

Frequencies

GnomAD3 genomes

AF:

0.000946

AC:

144

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00170

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000806

AC:

124

AN:

153928

Hom.:

AF XY:

0.000882

AC XY:

AN XY:

81674

show subpopulations

Gnomad AFR exome

AF:

0.000379

Gnomad AMR exome

AF:

0.000486

Gnomad ASJ exome

AF:

0.000471

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00163

Gnomad OTH exome

AF:

0.00185

GnomAD4 exome

AF:

0.00140

AC:

1955

AN:

1399052

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

904

AN XY:

690038

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

Gnomad4 AMR exome

AF:

0.000532

Gnomad4 ASJ exome

AF:

0.000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000609

Gnomad4 NFE exome

AF:

0.00169

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.000945

AC:

144

AN:

152358

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00171

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.000971

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00189

AC:

ExAC

AF:

0.000592

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2022

The c.1622A>G (p.E541G) alteration is located in exon 6 (coding exon 6) of the ANKUB1 gene. This alteration results from a A to G substitution at nucleotide position 1622, causing the glutamic acid (E) at amino acid position 541 to be replaced by a glycine (G). 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

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.38

M_CAP

Benign

0.011

MetaRNN

Benign

0.0089

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.64

REVEL

Benign

0.058

Sift

Uncertain

0.0070

Sift4G

Pathogenic

0.0

Vest4

0.11

MVP

0.067

ClinPred

0.046

GERP RS

3.1

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

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