Genetic Variant ZFTA:p.Gly247Asp (chr11-63765152-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001144936.2(ZFTA):c.740G>A(p.Gly247Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000627 in 1,545,920 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000045 ( 1 hom. )

Consequence

ZFTA
NM_001144936.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

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]

ZFTA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.03084454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFTA	NM_001144936.2 link	c.740G>A	p.Gly247Asp	missense_variant	Exon 3 of 5	ENST00000433688.2	NP_001138408.1	C9JLR9
ZFTA	XM_047427478.1 link	c.740G>A	p.Gly247Asp	missense_variant	Exon 3 of 4		XP_047283434.1
ZFTA	XM_047427477.1 link	c.638-554G>A		intron_variant	Intron 2 of 3		XP_047283433.1
ZFTA	XM_024448662.2 link	c.637+655G>A		intron_variant	Intron 2 of 2		XP_024304430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZFTA	ENST00000433688.2 link	c.740G>A	p.Gly247Asp	missense_variant	Exon 3 of 5	5	NM_001144936.2	ENSP00000482180.1	C9JLR9
ZFTA	ENST00000338498.6 link	c.154+655G>A		intron_variant	Intron 1 of 1	1		ENSP00000483097.1	A0A087X051
ZFTA	ENST00000445014.3 link	c.248G>A	p.Gly83Asp	missense_variant	Exon 2 of 4	5		ENSP00000478462.1	A0A087WU89

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000800

AC:

AN:

137444

Hom.:

AF XY:

0.0000402

AC XY:

AN XY:

74576

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.0000830

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000210

Gnomad OTH exome

AF:

0.000251

GnomAD4 exome

AF:

0.0000452

AC:

AN:

1393656

Hom.:

Cov.:

AF XY:

0.0000451

AC XY:

AN XY:

687322

show subpopulations

Gnomad4 AFR exome

AF:

0.000799

Gnomad4 AMR exome

AF:

0.000198

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:

0.0000186

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

AF:

0.000223

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.000332

ExAC

AF:

0.0000509

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.740G>A (p.G247D) alteration is located in exon 3 (coding exon 3) of the C11orf95 gene. This alteration results from a G to A substitution at nucleotide position 740, causing the glycine (G) at amino acid position 247 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

0.14

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0057

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.58

MetaRNN

Benign

0.031

MutationAssessor

Benign

0.97

Sift4G

Benign

0.34

Polyphen

0.0020

Vest4

0.20

MVP

0.061

GERP RS

3.1

Varity_R

0.11

gMVP

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over