6-33416723-C-T

Position:

• chr6-33416723-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001014840.2(CUTA):​c.467G>A​(p.Gly156Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CUTA NM_001014840.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.913

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUTA	NM_001014840.2	c.467G>A	p.Gly156Glu	missense_variant	6/6	ENST00000488034.6	NP_001014840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUTA	ENST00000488034.6	c.467G>A	p.Gly156Glu	missense_variant	6/6	2	NM_001014840.2	ENSP00000417544	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Dec 21, 2022

The c.524G>A (p.G175E) alteration is located in exon 6 (coding exon 6) of the CUTA gene. This alteration results from a G to A substitution at nucleotide position 524, causing the glycine (G) at amino acid position 175 to be replaced by a glutamic acid (E). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	.;.;D;.;.;.
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.97	D;D;D;.;.;.
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.91	D;D;D;D;D;D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Pathogenic	4.3	.;.;H;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-7.6	D;.;D;.;D;D
REVEL	Pathogenic	0.81
Sift	Pathogenic	0.0	D;.;D;.;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D
Polyphen		1.0	D;.;D;.;.;.
Vest4		0.83
MutPred		0.76		.;.;Gain of solvent accessibility (P = 0.024);.;.;.;
MVP		0.67
MPC		1.0
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.90
gMVP		0.55

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: chr6-33384500;