Variant 5-75080602-G-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_001372053.1(ANKRD31):c.5613C>G(p.Asn1871Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000276 in 1,522,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ANKRD31
NM_001372053.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.656

Variant links:

Genes affected

ANKRD31 (HGNC:26853): (ankyrin repeat domain 31) This gene encodes a protein containing multiple ankyrin repeats. Ankyrin domains function in protein-protein interactions in a variety of cellular processes. Mutations in this gene are associated with a Rett syndrome (RTT)-like phenotype. [provided by RefSeq, Apr 2017]

ANKRD31 links:

ANKRD31 (HGNC:):

ANKRD31 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=0.022960663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD31	NM_001372053.1 linkuse as main transcript	c.5613C>G	p.Asn1871Lys	missense_variant	25/26	ENST00000506364.6	NP_001358982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD31	ENST00000506364.6 linkuse as main transcript	c.5613C>G	p.Asn1871Lys	missense_variant	25/26	5	NM_001372053.1	ENSP00000427262.2		D6RJB7

Frequencies

GnomAD3 genomes

AF:

0.000186

AC:

AN:

150782

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000684

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000456

AC:

AN:

131514

Hom.:

AF XY:

0.0000286

AC XY:

AN XY:

69930

show subpopulations

Gnomad AFR exome

AF:

0.000822

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000102

AC:

AN:

1372138

Hom.:

Cov.:

AF XY:

0.0000104

AC XY:

AN XY:

676264

show subpopulations

Gnomad4 AFR exome

AF:

0.000420

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000186

AC:

AN:

150782

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

73534

show subpopulations

Gnomad4 AFR

AF:

0.000684

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000196

ExAC

AF:

0.000102

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

May 24, 2024

The c.5442C>G (p.N1814K) alteration is located in exon 24 (coding exon 24) of the ANKRD31 gene. This alteration results from a C to G substitution at nucleotide position 5442, causing the asparagine (N) at amino acid position 1814 to be replaced by a lysine (K). 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

0.12

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.0012

.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.41

.;N

REVEL

Benign

0.030

Sift

Uncertain

0.0030

.;D

Sift4G

Benign

0.13

T;T

Vest4

0.20

MutPred

0.19

.;Gain of ubiquitination at N1814 (P = 0.0022);

MVP

0.099

ClinPred

0.048

GERP RS

0.40

Varity_R

0.072

gMVP

0.027

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: 37

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