Variant 15-79293570-A-G 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_001146341.2(ANKRD34C):c.286A>G(p.Arg96Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000552 in 1,551,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 0 hom. )

Consequence

ANKRD34C
NM_001146341.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

ANKRD34C (HGNC:33888): (ankyrin repeat domain 34C)

ANKRD34C 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=0.015142888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD34C	NM_001146341.2 linkuse as main transcript	c.286A>G	p.Arg96Gly	missense_variant	2/2	ENST00000421388.4	NP_001139813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD34C	ENST00000421388.4 linkuse as main transcript	c.286A>G	p.Arg96Gly	missense_variant	2/2		NM_001146341.2	ENSP00000401089	P1

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000383

AC:

AN:

153944

Hom.:

AF XY:

0.000379

AC XY:

AN XY:

81700

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000243

Gnomad ASJ exome

AF:

0.000707

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.0000655

Gnomad NFE exome

AF:

0.000722

Gnomad OTH exome

AF:

0.000462

GnomAD4 exome

AF:

0.000574

AC:

803

AN:

1399384

Hom.:

Cov.:

AF XY:

0.000594

AC XY:

410

AN XY:

690204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000196

Gnomad4 ASJ exome

AF:

0.00171

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000142

Gnomad4 NFE exome

AF:

0.000667

Gnomad4 OTH exome

AF:

0.000448

GnomAD4 genome

AF:

0.000354

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000606

Hom.:

Bravo

AF:

0.000363

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000306

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

Sep 01, 2021

The c.286A>G (p.R96G) alteration is located in exon 2 (coding exon 1) of the ANKRD34C gene. This alteration results from a A to G substitution at nucleotide position 286, causing the arginine (R) at amino acid position 96 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.22

DEOGEN2

Benign

0.011

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.70

M_CAP

Benign

0.0043

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.3

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.0

REVEL

Benign

0.089

Sift

Benign

0.37

Sift4G

Benign

0.33

Polyphen

0.0010

Vest4

0.099

MVP

0.072

ClinPred

0.030

GERP RS

-1.0

Varity_R

0.052

gMVP

0.76

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