11-63764292-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001144936.2(ZFTA):​c.1331G>A​(p.Gly444Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000385 in 1,297,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000039 ( 0 hom. )

Consequence

ZFTA
NM_001144936.2 missense

Scores

2
2
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64
Variant links:
Genes affected
ZFTA (HGNC:28449): (zinc finger translocation associated) Predicted to be involved in negative regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34630272).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZFTANM_001144936.2 linkc.1331G>A p.Gly444Asp missense_variant Exon 4 of 5 ENST00000433688.2 NP_001138408.1 C9JLR9
ZFTAXM_047427477.1 linkc.944G>A p.Gly315Asp missense_variant Exon 3 of 4 XP_047283433.1
ZFTAXM_047427478.1 linkc.1025-423G>A intron_variant Intron 3 of 3 XP_047283434.1
ZFTAXM_024448662.2 linkc.638-423G>A intron_variant Intron 2 of 2 XP_024304430.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZFTAENST00000433688.2 linkc.1331G>A p.Gly444Asp missense_variant Exon 4 of 5 5 NM_001144936.2 ENSP00000482180.1 C9JLR9
ZFTAENST00000338498.6 linkc.155-423G>A intron_variant Intron 1 of 1 1 ENSP00000483097.1 A0A087X051
ZFTAENST00000445014.3 linkc.716G>A p.Gly239Asp missense_variant Exon 4 of 4 5 ENSP00000478462.1 A0A087WU89

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000385
AC:
5
AN:
1297024
Hom.:
0
Cov.:
32
AF XY:
0.00000469
AC XY:
3
AN XY:
639444
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000282
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000289
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1331G>A (p.G444D) alteration is located in exon 4 (coding exon 4) of the C11orf95 gene. This alteration results from a G to A substitution at nucleotide position 1331, causing the glycine (G) at amino acid position 444 to be replaced by an aspartic acid (D). 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
0.29
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
26
DANN
Uncertain
0.98
DEOGEN2
Benign
0.059
T
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.78
T
MetaRNN
Benign
0.35
T
MutationAssessor
Uncertain
2.3
M
Sift4G
Benign
0.35
T
Polyphen
1.0
D
Vest4
0.41
MVP
0.061
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.6
Varity_R
0.34
gMVP
0.56

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: chr11-63531764; API