Genetic Variant NM_001372053.1:c.5086G>A (chr5-75104473-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001372053.1(ANKRD31):c.5086G>A(p.Gly1696Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000065 in 1,384,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

ANKRD31
NM_001372053.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.177

Publications

0 publications found

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06157735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372053.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD31	NM_001372053.1	MANE Select	c.5086G>A	p.Gly1696Arg	missense	Exon 22 of 26	NP_001358982.1	D6RJB7
	ANKRD31	NM_001164443.1		c.4915G>A	p.Gly1639Arg	missense	Exon 21 of 25	NP_001157915.1	Q8N7Z5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD31	ENST00000506364.6	TSL:5 MANE Select	c.5086G>A	p.Gly1696Arg	missense	Exon 22 of 26	ENSP00000427262.2	D6RJB7
ANKRD31	ENST00000274361.3	TSL:5	c.4915G>A	p.Gly1639Arg	missense	Exon 21 of 25	ENSP00000274361.3	Q8N7Z5
ANKRD31	ENST00000504022.1	TSL:5	n.1876G>A		non_coding_transcript_exon	Exon 10 of 14

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000650

AC:

AN:

1384916

Hom.:

Cov.:

AF XY:

0.00000878

AC XY:

AN XY:

683378

show subpopulations

African (AFR)

AF:

0.000127

AC:

AN:

31594

American (AMR)

AF:

0.00

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

35726

South Asian (SAS)

AF:

0.00

AC:

AN:

79232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35002

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078876

Other (OTH)

AF:

0.0000691

AC:

AN:

57912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.3

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0029

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.53

M_CAP

Benign

0.025

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

PhyloP100

-0.18

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.97

REVEL

Benign

0.042

Sift

Benign

0.45

Sift4G

Benign

0.15

Vest4

0.088

MutPred

0.41

Gain of catalytic residue at G1639 (P = 0.0107)

MVP

0.28

ClinPred

0.055

GERP RS

-3.7

Varity_R

0.040

gMVP

0.055

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over