Genetic Variant ZFTA:p.Ser320Arg (chr11-63764934-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_001144936.2(ZFTA):c.958A>C(p.Ser320Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000043 in 1,393,874 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: 0.0000043 ( 0 hom. )

Consequence

ZFTA
NM_001144936.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.469

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:

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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=0.33120388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFTA	NM_001144936.2 link	c.958A>C	p.Ser320Arg	missense_variant	Exon 3 of 5	ENST00000433688.2	NP_001138408.1	C9JLR9
ZFTA	XM_047427478.1 link	c.958A>C	p.Ser320Arg	missense_variant	Exon 3 of 4		XP_047283434.1
ZFTA	XM_047427477.1 link	c.638-336A>C		intron_variant	Intron 2 of 3		XP_047283433.1
ZFTA	XM_024448662.2 link	c.637+873A>C		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.958A>C	p.Ser320Arg	missense_variant	Exon 3 of 5	5	NM_001144936.2	ENSP00000482180.1	C9JLR9
ZFTA	ENST00000338498.6 link	c.154+873A>C		intron_variant	Intron 1 of 1	1		ENSP00000483097.1	A0A087X051
ZFTA	ENST00000445014.3 link	c.358-15A>C		intron_variant	Intron 2 of 3	5		ENSP00000478462.1	A0A087WU89

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000733

AC:

AN:

136414

Hom.:

AF XY:

0.00

AC XY:

AN XY:

73986

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000961

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000430

AC:

AN:

1393874

Hom.:

Cov.:

AF XY:

0.00000436

AC XY:

AN XY:

687494

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000112

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 15, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.958A>C (p.S320R) alteration is located in exon 3 (coding exon 3) of the C11orf95 gene. This alteration results from a A to C substitution at nucleotide position 958, causing the serine (S) at amino acid position 320 to be replaced by an arginine (R). 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

Uncertain

0.42

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.025

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.53

MetaRNN

Benign

0.33

MutationAssessor

Benign

1.4

Sift4G

Uncertain

0.044

Polyphen

0.99

Vest4

0.43

MVP

0.072

GERP RS

2.6

Varity_R

0.34

gMVP

0.63

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