Genetic Variant NM_152643.8:c.171C>T (chr10-133167449-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_152643.8(KNDC1):c.171C>T(p.Ala57Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 1,606,108 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0064 ( 36 hom. )

Consequence

KNDC1
NM_152643.8 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.51

Variant links:

Genes affected

KNDC1 (HGNC:29374): (kinase non-catalytic C-lobe domain containing 1) The protein encoded by this gene is a Ras guanine nucleotide exchange factor that appears to negatively regulate dendritic growth in the brain. Knockdown of this gene in senescent umbilical vein endothelial cells partially reversed the senescence, showing that this gene could potentially be targeted by anti-aging therapies. [provided by RefSeq, Dec 2016]

KNDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 10-133167449-C-T is Benign according to our data. Variant chr10-133167449-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640998.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.51 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KNDC1	NM_152643.8 link	c.171C>T	p.Ala57Ala	synonymous_variant	Exon 2 of 30	ENST00000304613.8	NP_689856.6	Q76NI1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KNDC1	ENST00000304613.8 link	c.171C>T	p.Ala57Ala	synonymous_variant	Exon 2 of 30	1	NM_152643.8	ENSP00000304437.3		Q76NI1-1

Frequencies

GnomAD3 genomes

AF:

0.00434

AC:

661

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00744

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00389

AC:

905

AN:

232690

Hom.:

AF XY:

0.00408

AC XY:

515

AN XY:

126356

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.000696

Gnomad ASJ exome

AF:

0.000209

Gnomad EAS exome

AF:

0.000574

Gnomad SAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.00160

Gnomad NFE exome

AF:

0.00735

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00635

AC:

9236

AN:

1453782

Hom.:

Cov.:

AF XY:

0.00604

AC XY:

4367

AN XY:

722442

show subpopulations

Gnomad4 AFR exome

AF:

0.000808

Gnomad4 AMR exome

AF:

0.000685

Gnomad4 ASJ exome

AF:

0.000232

Gnomad4 EAS exome

AF:

0.000229

Gnomad4 SAS exome

AF:

0.00126

Gnomad4 FIN exome

AF:

0.00242

Gnomad4 NFE exome

AF:

0.00776

Gnomad4 OTH exome

AF:

0.00541

GnomAD4 genome

AF:

0.00434

AC:

661

AN:

152326

Hom.:

Cov.:

AF XY:

0.00418

AC XY:

311

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00744

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00389

Hom.:

Bravo

AF:

0.00424

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KNDC1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.5

DANN

Benign

0.80

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