Genetic Variant UNC93A:p.Ala220Val (chr6-167303952-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018974.4(UNC93A):c.659C>T(p.Ala220Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00492 in 1,613,430 control chromosomes in the GnomAD database, including 349 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 174 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 175 hom. )

Consequence

UNC93A
NM_018974.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.05

Variant links:

Genes affected

UNC93A (HGNC:12570): (unc-93 homolog A) Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

UNC93A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014178157).

BP6

Variant 6-167303952-C-T is Benign according to our data. Variant chr6-167303952-C-T is described in ClinVar as [Benign]. Clinvar id is 768119.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC93A	NM_018974.4 link	c.659C>T	p.Ala220Val	missense_variant	Exon 5 of 8	ENST00000230256.8	NP_061847.2	Q86WB7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC93A	ENST00000230256.8 link	c.659C>T	p.Ala220Val	missense_variant	Exon 5 of 8	1	NM_018974.4	ENSP00000230256.3		Q86WB7-1
UNC93A	ENST00000366829.2 link	c.533C>T	p.Ala178Val	missense_variant	Exon 4 of 7	1		ENSP00000355794.2		Q86WB7-2

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3928

AN:

151420

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0912

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00791

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000629

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0178

GnomAD3 exomes

AF:

0.00674

AC:

1679

AN:

249050

Hom.:

AF XY:

0.00471

AC XY:

635

AN XY:

134816

show subpopulations

Gnomad AFR exome

AF:

0.0925

Gnomad AMR exome

AF:

0.00364

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000180

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00274

AC:

4005

AN:

1461892

Hom.:

175

Cov.:

AF XY:

0.00236

AC XY:

1717

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0974

Gnomad4 AMR exome

AF:

0.00418

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.00644

GnomAD4 genome

AF:

0.0260

AC:

3937

AN:

151538

Hom.:

174

Cov.:

AF XY:

0.0253

AC XY:

1871

AN XY:

74022

show subpopulations

Gnomad4 AFR

AF:

0.0912

Gnomad4 AMR

AF:

0.00790

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000629

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0176

Alfa

AF:

0.00454

Hom.:

Bravo

AF:

0.0308

ESP6500AA

AF:

0.0860

AC:

379

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00839

AC:

1018

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.49

DANN

Benign

0.15

DEOGEN2

Benign

0.00086

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00099

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-2.1

N;.

PrimateAI

Benign

0.25

PROVEAN

Benign

3.0

N;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;.

Vest4

0.044

MVP

0.18

MPC

0.24

ClinPred

0.0028

GERP RS

2.2

Varity_R

0.018

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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