18-62187660-C-G

Position:

• chr18-62187660-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001346231.2(RELCH):​c.155C>G​(p.Ala52Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,408,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RELCH NM_001346231.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.097050846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELCH	NM_001346231.2	c.155C>G	p.Ala52Gly	missense_variant	1/29	ENST00000644646.2	NP_001333160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELCH	ENST00000644646.2	c.155C>G	p.Ala52Gly	missense_variant	1/29		NM_001346231.2	ENSP00000494314.1
RELCH	ENST00000398130.6	c.155C>G	p.Ala52Gly	missense_variant	1/29	1		ENSP00000381198.2
RELCH	ENST00000256858.10	c.155C>G	p.Ala52Gly	missense_variant	1/30	5		ENSP00000256858.5
RELCH	ENST00000587725.5	n.155C>G		non_coding_transcript_exon_variant	1/22	2		ENSP00000468816.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1408212 Hom.: 0 Cov.: 31 AF XY: 0.00000288 AC XY: 2 AN XY: 694010

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: 0.0000253

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.155C>G (p.A52G) alteration is located in exon 1 (coding exon 1) of the KIAA1468 gene. This alteration results from a C to G substitution at nucleotide position 155, causing the alanine (A) at amino acid position 52 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	0.073
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	.;.;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.097	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.75	.;N;N
REVEL	Benign	0.019
Sift	Benign	0.32	.;T;T
Sift4G	Benign	0.50	.;T;T
Polyphen		0.0010, 0.0030	.;B;B
Vest4		0.19, 0.10
MutPred		0.15		Gain of glycosylation at S51 (P = 0.0436);Gain of glycosylation at S51 (P = 0.0436);Gain of glycosylation at S51 (P = 0.0436);
MVP		0.12
MPC		0.71
ClinPred		0.23	T
GERP RS		3.0
Varity_R		0.15
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-59854893;