Genetic Variant ANKRD31:p.Cys1912Phe (chr5-75068577-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001372053.1(ANKRD31):c.5735G>T(p.Cys1912Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000196 in 1,527,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

ANKRD31
NM_001372053.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD31	NM_001372053.1 link	c.5735G>T	p.Cys1912Phe	missense_variant	Exon 26 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.5735G>T	p.Cys1912Phe	missense_variant	Exon 26 of 26	5	NM_001372053.1	ENSP00000427262.2		D6RJB7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1375340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

678042

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000290

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5564G>T (p.C1855F) alteration is located in exon 25 (coding exon 25) of the ANKRD31 gene. This alteration results from a G to T substitution at nucleotide position 5564, causing the cysteine (C) at amino acid position 1855 to be replaced by a phenylalanine (F). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.081

.;T

Eigen

Benign

0.12

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.1

.;M

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-4.2

.;D

REVEL

Benign

0.25

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.48

MutPred

0.74

.;Loss of catalytic residue at P1854 (P = 0.0244);

MVP

0.58

ClinPred

0.98

GERP RS

4.1

Varity_R

0.61

gMVP

0.12

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