dbSNP rs374469503: CUTA:p.Arg86Ser (chr6-33417310-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001014840.2(CUTA):c.258G>T(p.Arg86Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R86R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CUTA
NM_001014840.2 missense, splice_region

Scores

Splicing: ADA: 0.9952

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.94

Variant links:

Genes affected

CUTA (HGNC:21101): (cutA divalent cation tolerance homolog) Enables enzyme binding activity. Involved in protein localization. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CUTA links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.818

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUTA	NM_001014840.2 link	c.258G>T	p.Arg86Ser	missense_variant, splice_region_variant	Exon 3 of 6	ENST00000488034.6	NP_001014840.1	O60888-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUTA	ENST00000488034.6 link	c.258G>T	p.Arg86Ser	missense_variant, splice_region_variant	Exon 3 of 6	2	NM_001014840.2	ENSP00000417544.1		O60888-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251452

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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:

0.00000205

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

.;.;T;.;T;.;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.064

FATHMM_MKL

Benign

0.59

LIST_S2

Pathogenic

0.98

D;D;D;.;D;D;.;.

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.82

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.3

.;.;M;.;.;.;.;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.5

D;.;D;.;D;D;D;D

REVEL

Benign

0.27

Sift

Benign

0.065

T;.;T;.;T;T;T;T

Sift4G

Benign

0.16

T;T;T;T;T;T;T;T

Polyphen

0.12

B;.;B;.;.;.;.;.

Vest4

0.77

MutPred

0.66

.;.;Loss of MoRF binding (P = 0.0269);.;.;Loss of MoRF binding (P = 0.0269);.;.;

MVP

0.57

MPC

0.33

ClinPred

0.83

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.87

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.90

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over