11-63764292-C-T

Variant names:

• chr11-63764292-C-T
• NM_001144936.2:c.1331G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64

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]

ACMG classification

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
ZFTA	NM_001144936.2	c.1331G>A	p.Gly444Asp	missense_variant	Exon 4 of 5	ENST00000433688.2	NP_001138408.1
ZFTA	XM_047427477.1	c.944G>A	p.Gly315Asp	missense_variant	Exon 3 of 4		XP_047283433.1
ZFTA	XM_047427478.1	c.1025-423G>A		intron_variant	Intron 3 of 3		XP_047283434.1
ZFTA	XM_024448662.2	c.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
ZFTA	ENST00000433688.2	c.1331G>A	p.Gly444Asp	missense_variant	Exon 4 of 5	5	NM_001144936.2	ENSP00000482180.1
ZFTA	ENST00000338498.6	c.155-423G>A		intron_variant	Intron 1 of 1	1		ENSP00000483097.1
ZFTA	ENST00000445014.3	c.716G>A	p.Gly239Asp	missense_variant	Exon 4 of 4	5		ENSP00000478462.1

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

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

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;