Genetic Variant GARIN5A:p.Pro55Thr (chr19-50476226-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001308429.2(GARIN5A):c.163C>A(p.Pro55Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P55S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

GARIN5A
NM_001308429.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.287

Publications

0 publications found

Variant links:

Genes affected

GARIN5A (HGNC:25107): (golgi associated RAB2 interactor 5A)

GARIN5A links:

EMC10 (HGNC:27609): (ER membrane protein complex subunit 10) Contributes to membrane insertase activity. Involved in positive regulation of angiogenesis; positive regulation of endothelial cell proliferation; and protein insertion into ER membrane. Located in extracellular region. Is integral component of endoplasmic reticulum membrane. Part of EMC complex. [provided by Alliance of Genome Resources, Apr 2022]

EMC10 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with dysmorphic facies and variable seizures
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder
Inheritance: AR Classification: STRONG Submitted by: G2P
global developmental delay with or without impaired intellectual development
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

EMC10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0521729).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308429.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARIN5A	NM_001308429.2	MANE Select	c.163C>A	p.Pro55Thr	missense	Exon 1 of 5	NP_001295358.1	Q6IPT2-1
	GARIN5A	NM_138411.3		c.163C>A	p.Pro55Thr	missense	Exon 1 of 5	NP_612420.1	Q6IPT2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GARIN5A	ENST00000600100.6	TSL:1 MANE Select	c.163C>A	p.Pro55Thr	missense	Exon 1 of 5	ENSP00000472421.2	Q6IPT2-1
GARIN5A	ENST00000595790.5	TSL:1	c.163C>A	p.Pro55Thr	missense	Exon 1 of 5	ENSP00000471272.2	Q6IPT2-2
GARIN5A	ENST00000897783.1		c.163C>A	p.Pro55Thr	missense	Exon 1 of 5	ENSP00000567842.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000408

AC:

AN:

245244

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000920

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.4

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0036

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.34

M_CAP

Benign

0.0088

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

-0.29

PrimateAI

Benign

0.34

Sift4G

Pathogenic

0.0

Polyphen

0.0040

Vest4

0.18

MutPred

0.20

Loss of disorder (P = 0.0685)

MVP

0.055

MPC

0.72

ClinPred

0.053

GERP RS

-1.7

PromoterAI

0.081

Neutral

(source)

Varity_R

0.050

gMVP

0.19

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over