chr11-63764871-G-T

Position:

• chr11-63764871-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001144936.2(ZFTA):​c.1021C>A​(p.Pro341Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,340,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: ZFTA NM_001144936.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04623744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFTA	NM_001144936.2	c.1021C>A	p.Pro341Thr	missense_variant	3/5	ENST00000433688.2
ZFTA	XM_047427478.1	c.1021C>A	p.Pro341Thr	missense_variant	3/4
ZFTA	XM_024448662.2	c.637+936C>A		intron_variant
ZFTA	XM_047427477.1	c.638-273C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFTA	ENST00000433688.2	c.1021C>A	p.Pro341Thr	missense_variant	3/5	5	NM_001144936.2	P1
ZFTA	ENST00000338498.6	c.156+936C>A		intron_variant		1
ZFTA	ENST00000445014.3	c.409C>A	p.Pro137Thr	missense_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000373 AC: 5 AN: 1340132 Hom.: 0 Cov.: 31 AF XY: 0.00000152 AC XY: 1 AN XY: 656430

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: 0.00000284

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000509 Hom.: 0

Bravo AF: 0.00000378

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

Jun 25, 2021

The c.1021C>A (p.P341T) alteration is located in exon 3 (coding exon 3) of the C11orf95 gene. This alteration results from a C to A substitution at nucleotide position 1021, causing the proline (P) at amino acid position 341 to be replaced by a threonine (T). 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	0.062
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.0
DANN	Benign	0.81
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.046	T
MutationAssessor	Benign	1.5	L
Sift4G	Benign	0.071	T
Polyphen		0.0030	B
Vest4		0.087
MVP		0.055
GERP RS		-5.1
Varity_R		0.055
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs1462350481; hg19: chr11-63532343;