18-62187725-G-A

Position:

• chr18-62187725-G-A

Variant summary

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

The NM_001346231.2(RELCH):​c.220G>A​(p.Glu74Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RELCH NM_001346231.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.33

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=0.2263501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELCH	NM_001346231.2	c.220G>A	p.Glu74Lys	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.220G>A	p.Glu74Lys	missense_variant	1/29		NM_001346231.2	ENSP00000494314.1
RELCH	ENST00000398130.6	c.220G>A	p.Glu74Lys	missense_variant	1/29	1		ENSP00000381198.2
RELCH	ENST00000256858.10	c.220G>A	p.Glu74Lys	missense_variant	1/30	5		ENSP00000256858.5
RELCH	ENST00000587725.5	n.220G>A		non_coding_transcript_exon_variant	1/22	2		ENSP00000468816.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Oct 24, 2024

The c.220G>A (p.E74K) alteration is located in exon 1 (coding exon 1) of the KIAA1468 gene. This alteration results from a G to A substitution at nucleotide position 220, causing the glutamic acid (E) at amino acid position 74 to be replaced by a lysine (K). 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	0.15
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	.;.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.2	.;N;N
REVEL	Benign	0.016
Sift	Benign	0.16	.;T;T
Sift4G	Uncertain	0.040	.;D;D
Polyphen		0.18, 0.0	.;B;B
Vest4		0.32, 0.39
MutPred		0.27		Gain of ubiquitination at E74 (P = 0.0094);Gain of ubiquitination at E74 (P = 0.0094);Gain of ubiquitination at E74 (P = 0.0094);
MVP		0.093
MPC		0.85
ClinPred		0.84	D
GERP RS		4.3
Varity_R		0.24
gMVP		0.62

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: chr18-59854958;