11-65116809-C-G

Variant names:

• chr11-65116809-C-G
• NM_014205.4:c.845G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014205.4(ZNHIT2):​c.845G>C​(p.Gly282Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZNHIT2 NM_014205.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.87

Genes affected

ZNHIT2 (HGNC:1177): (zinc finger HIT-type containing 2) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16884243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNHIT2	NM_014205.4	c.845G>C	p.Gly282Ala	missense_variant	Exon 1 of 1	ENST00000310597.6	NP_055020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNHIT2	ENST00000310597.6	c.845G>C	p.Gly282Ala	missense_variant	Exon 1 of 1	6	NM_014205.4	ENSP00000308548.4
ZNHIT2	ENST00000528598.1	c.350G>C	p.Gly117Ala	missense_variant	Exon 2 of 2	3		ENSP00000436896.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.845G>C (p.G282A) alteration is located in exon 1 (coding exon 1) of the ZNHIT2 gene. This alteration results from a G to C substitution at nucleotide position 845, causing the glycine (G) at amino acid position 282 to be replaced by an alanine (A). 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	0.39
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	-0.0077
Eigen_PC	Benign	-0.028
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.29	N;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;T
Sift4G	Pathogenic	0.0	D;.
Polyphen		1.0	D;.
Vest4		0.14
MutPred		0.30		Loss of methylation at R284 (P = 0.1028);.;
MVP		0.19
MPC		1.5
ClinPred		0.78	D
GERP RS		4.7
Varity_R		0.10
gMVP		0.30

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-64884281;