Variant 1-145872809-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_144698.5(ANKRD35):c.1960C>G(p.Arg654Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0004 in 1,613,770 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00041 ( 3 hom. )

Consequence

ANKRD35
NM_144698.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Variant links:

Genes affected

ANKRD35 (HGNC:26323): (ankyrin repeat domain 35)

ANKRD35 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07716748).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD35	NM_144698.5 linkuse as main transcript	c.1960C>G	p.Arg654Gly	missense_variant	10/14	ENST00000355594.9	NP_653299.4	Q8N283-1B4DFX6
ANKRD35	NM_001280799.2 linkuse as main transcript	c.1690C>G	p.Arg564Gly	missense_variant	8/12		NP_001267728.1	F6XZD3B4DFX6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD35	ENST00000355594.9 linkuse as main transcript	c.1960C>G	p.Arg654Gly	missense_variant	10/14	2	NM_144698.5	ENSP00000347802.4		Q8N283-1
ANKRD35	ENST00000544626.2 linkuse as main transcript	c.1690C>G	p.Arg564Gly	missense_variant	8/12	5		ENSP00000442671.2		F6XZD3

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000523

AC:

131

AN:

250454

Hom.:

AF XY:

0.000509

AC XY:

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000603

Gnomad NFE exome

AF:

0.000982

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000412

AC:

602

AN:

1461608

Hom.:

Cov.:

AF XY:

0.000380

AC XY:

276

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000451

Gnomad4 NFE exome

AF:

0.000487

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.000283

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000268

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 09, 2024

The c.1960C>G (p.R654G) alteration is located in exon 10 (coding exon 10) of the ANKRD35 gene. This alteration results from a C to G substitution at nucleotide position 1960, causing the arginine (R) at amino acid position 654 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

0.082

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

.;T

LIST_S2

Benign

0.64

.;T

MetaRNN

Benign

0.077

T;T

PROVEAN

Benign

-0.85

N;.

Sift

Benign

0.080

T;.

Sift4G

Benign

0.14

T;T

Vest4

0.14

gMVP

0.58

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