11-63765131-C-G

Variant names:

• chr11-63765131-C-G
• rs776171287
• NM_001144936.2:c.761G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144936.2(ZFTA):​c.761G>C​(p.Arg254Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,395,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R254Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: ZFTA NM_001144936.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10131022).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144936.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFTA	NM_001144936.2	MANE Select	c.761G>C	p.Arg254Pro	missense	Exon 3 of 5	NP_001138408.1	C9JLR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFTA	ENST00000433688.2	TSL:5 MANE Select	c.761G>C	p.Arg254Pro	missense	Exon 3 of 5	ENSP00000482180.1	C9JLR9
	ZFTA	ENST00000338498.6	TSL:1	c.154+676G>C		intron	N/A	ENSP00000483097.1	A0A087X051
	ZFTA	ENST00000918477.1		c.761G>C	p.Arg254Pro	missense	Exon 3 of 4	ENSP00000588536.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000717 AC: 1 AN: 139546 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000206

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000287 AC: 4 AN: 1395370 Hom.: 0 Cov.: 32 AF XY: 0.00000291 AC XY: 2 AN XY: 688200

African (AFR) AF: 0.00 AC: 0 AN: 31446

American (AMR) AF: 0.00 AC: 0 AN: 35628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25108

East Asian (EAS) AF: 0.00 AC: 0 AN: 35650

South Asian (SAS) AF: 0.00 AC: 0 AN: 79114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4742

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1078202

Other (OTH) AF: 0.00 AC: 0 AN: 57786

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	21
DANN	Benign	0.88
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.10	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.75
Sift4G	Uncertain	0.043	D
Polyphen		0.0040	B
Vest4		0.32
MVP		0.12
GERP RS		2.0
Varity_R		0.31
gMVP		0.83
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs776171287; hg19: chr11-63532603;