chr7-64336358-G-C

Position:

• chr7-64336358-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001170905.3(ZNF736):​c.103G>C​(p.Glu35Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF736 NM_001170905.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46

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]

ZNF736 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF736	NM_001170905.3	c.103G>C	p.Glu35Gln	missense_variant	2/4	ENST00000423484.3	NP_001164376.1
ZNF736	NM_001294255.2	c.103G>C	p.Glu35Gln	missense_variant	2/3		NP_001281184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF736	ENST00000423484.3	c.103G>C	p.Glu35Gln	missense_variant	2/4	2	NM_001170905.3	ENSP00000400852.1
ZNF736	ENST00000355095.8	c.103G>C	p.Glu35Gln	missense_variant	3/5	5		ENSP00000347210.4
ZNF736	ENST00000488621.1	n.240G>C		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 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

Aug 21, 2024

The c.103G>C (p.E35Q) alteration is located in exon 3 (coding exon 2) of the ZNF736 gene. This alteration results from a G to C substitution at nucleotide position 103, causing the glutamic acid (E) at amino acid position 35 to be replaced by a glutamine (Q). 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	0.41
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T;T
Eigen	Benign	0.14
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.69	T;.
M_CAP	Benign	0.00084	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	4.0	H;H
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.021	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.97	D;D
Vest4		0.38
MutPred		0.79		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.40
MPC		0.19
ClinPred		0.90	D
GERP RS		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.28
gMVP		0.072

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: rs1457274601; hg19: chr7-63796736;