7-64348938-C-A

Position:

• chr7-64348938-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001170905.3(ZNF736):​c.1075C>A​(p.His359Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,446,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF736 NM_001170905.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13

Genes affected

ZNF736 (HGNC:32467): (zinc finger protein 736) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF736	NM_001170905.3	c.1075C>A	p.His359Asn	missense_variant	4/4	ENST00000423484.3	NP_001164376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF736	ENST00000423484.3	c.1075C>A	p.His359Asn	missense_variant	4/4	2	NM_001170905.3	ENSP00000400852	P1
ZNF736	ENST00000355095.8	c.1075C>A	p.His359Asn	missense_variant	5/5	5		ENSP00000347210	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446286 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 718158

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: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

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

Dec 13, 2021

The c.1075C>A (p.H359N) alteration is located in exon 5 (coding exon 4) of the ZNF736 gene. This alteration results from a C to A substitution at nucleotide position 1075, causing the histidine (H) at amino acid position 359 to be replaced by an asparagine (N). 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	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.24	T;T
Eigen	Uncertain	0.23
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.54	T;.
M_CAP	Benign	0.0017	T
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Pathogenic	3.9	H;H
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-6.6	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.99	D;D
Vest4		0.34
MutPred		0.81		Loss of catalytic residue at K360 (P = 0.0265);Loss of catalytic residue at K360 (P = 0.0265);
MVP		0.83
MPC		0.30
ClinPred		0.99	D
GERP RS		1.2
Varity_R		0.46
gMVP		0.044

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: chr7-63809316;