Variant 13-106567723-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018011.4(ARGLU1):c.197C>A(p.Ser66Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ARGLU1
NM_018011.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.35

Variant links:

Genes affected

ARGLU1 (HGNC:25482): (arginine and glutamate rich 1) Enables cadherin binding activity. Located in cytosol; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ARGLU1 links:

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ACMG classification

Classification made for transcript

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=0.1424213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARGLU1	NM_018011.4 linkuse as main transcript	c.197C>A	p.Ser66Tyr	missense_variant	1/4	ENST00000400198.8	NP_060481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARGLU1	ENST00000400198.8 linkuse as main transcript	c.197C>A	p.Ser66Tyr	missense_variant	1/4	1	NM_018011.4	ENSP00000383059	P1	Q9NWB6-1
ARGLU1	ENST00000472226.2 linkuse as main transcript	n.415C>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000830

AC:

AN:

241030

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132092

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000114

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457358

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725004

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000832

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

May 24, 2024

The c.197C>A (p.S66Y) alteration is located in exon 1 (coding exon 1) of the ARGLU1 gene. This alteration results from a C to A substitution at nucleotide position 197, causing the serine (S) at amino acid position 66 to be replaced by a tyrosine (Y). 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

0.20

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.048

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.00048

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.74

M_CAP

Benign

0.052

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.88

REVEL

Benign

0.064

Sift

Benign

0.30

Sift4G

Benign

1.0

Polyphen

0.042

Vest4

0.33

MutPred

0.31

Loss of loop (P = 0.0804);

MVP

0.15

MPC

2.2

ClinPred

0.22

GERP RS

3.9

Varity_R

0.11

gMVP

0.44

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