Variant 18-62187536-A-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_001346231.2(RELCH):c.31A>C(p.Ser11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000535 in 1,514,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

RELCH
NM_001346231.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

Variant links:

Genes affected

RELCH (HGNC:29289): (RAB11 binding and LisH domain, coiled-coil and HEAT repeat containing) Involved in intracellular cholesterol transport. Located in recycling endosome and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

RELCH links:

RELCH (HGNC:):

RELCH 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=0.16513386).

BS2

High AC in GnomAdExome4 at 79 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELCH	NM_001346231.2 linkuse as main transcript	c.31A>C	p.Ser11Arg	missense_variant	1/29	ENST00000644646.2	NP_001333160.1	A0A2R8Y566

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RELCH	ENST00000644646.2 linkuse as main transcript	c.31A>C	p.Ser11Arg	missense_variant	1/29		NM_001346231.2	ENSP00000494314.1	A0A2R8Y566
RELCH	ENST00000398130.6 linkuse as main transcript	c.31A>C	p.Ser11Arg	missense_variant	1/29	1		ENSP00000381198.2	Q9P260-1
RELCH	ENST00000256858.10 linkuse as main transcript	c.31A>C	p.Ser11Arg	missense_variant	1/30	5		ENSP00000256858.5	Q9P260-2
RELCH	ENST00000587725.5 linkuse as main transcript	n.31A>C		non_coding_transcript_exon_variant	1/22	2		ENSP00000468816.1	A0A075B785

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152220

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000113

AC:

AN:

176678

Hom.:

AF XY:

0.0000214

AC XY:

AN XY:

93400

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000662

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000580

AC:

AN:

1362292

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

666614

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000851

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000564

Gnomad4 OTH exome

AF:

0.0000357

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000134

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000171

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

Aug 31, 2022

The c.31A>C (p.S11R) alteration is located in exon 1 (coding exon 1) of the KIAA1468 gene. This alteration results from a A to C substitution at nucleotide position 31, causing the serine (S) at amino acid position 11 to be replaced by an arginine (R). 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

0.47

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

.;.;T

Eigen

Benign

0.037

Eigen_PC

Benign

0.078

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.1

.;N;N

REVEL

Benign

0.056

Sift

Uncertain

0.0060

.;D;D

Sift4G

Uncertain

0.045

.;D;T

Polyphen

1.0, 0.73

.;D;P

Vest4

0.26, 0.28

MutPred

0.21

Loss of glycosylation at S11 (P = 0.0017);Loss of glycosylation at S11 (P = 0.0017);Loss of glycosylation at S11 (P = 0.0017);

MVP

0.082

MPC

1.1

ClinPred

0.55

GERP RS

3.1

Varity_R

0.35

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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