dbSNP rs140882867: ANKRD31:p.Gly1640Cys (chr5-75104641-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001372053.1(ANKRD31):c.4918G>T(p.Gly1640Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,383,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. G1640S) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANKRD31
NM_001372053.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.440

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30473793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD31	NM_001372053.1 link	c.4918G>T	p.Gly1640Cys	missense_variant	Exon 22 of 26	ENST00000506364.6	NP_001358982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD31	ENST00000506364.6 link	c.4918G>T	p.Gly1640Cys	missense_variant	Exon 22 of 26	5	NM_001372053.1	ENSP00000427262.2		D6RJB7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000711

AC:

AN:

140694

AF XY:

0.00

show subpopulations

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:

0.0000173

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1383742

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

682708

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31492

American (AMR)

AF:

0.00

AC:

AN:

35508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25154

East Asian (EAS)

AF:

0.00

AC:

AN:

35714

South Asian (SAS)

AF:

0.00

AC:

AN:

78898

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078440

Other (OTH)

AF:

0.0000173

AC:

AN:

57852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

.;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.9

.;M

PhyloP100

0.44

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-3.5

.;D

REVEL

Benign

0.11

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.018

D;D

Vest4

0.44

MutPred

0.65

.;Gain of methylation at K1584 (P = 0.0303);

MVP

0.52

ClinPred

0.50

GERP RS

2.9

Varity_R

0.27

gMVP

0.055

Mutation Taster

=97/3

polymorphism

(source)

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 for variant 5:75104641 C>A . It may be empty.

rs140882867

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over