10-79386438-G-T

Position:

• chr10-79386438-G-T

Variant summary

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

The NM_153367.4(ZCCHC24):​c.633C>A​(p.Asp211Glu) 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: 33)
• Consequence: ZCCHC24 NM_153367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.01

Genes affected

ZCCHC24 (HGNC:26911): (zinc finger CCHC-type containing 24) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

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=0.22692883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZCCHC24	NM_153367.4	c.633C>A	p.Asp211Glu	missense_variant	4/4	ENST00000372336.4
ZCCHC24	XM_011539452.4	c.423C>A	p.Asp141Glu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZCCHC24	ENST00000372336.4	c.633C>A	p.Asp211Glu	missense_variant	4/4	1	NM_153367.4	P1
	ENST00000438554.2	n.259+3852G>T		intron_variant, non_coding_transcript_variant		5
ZCCHC24	ENST00000372333.3	c.454C>A	p.Arg152=	synonymous_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 08, 2022

The c.633C>A (p.D211E) alteration is located in exon 4 (coding exon 4) of the ZCCHC24 gene. This alteration results from a C to A substitution at nucleotide position 633, causing the aspartic acid (D) at amino acid position 211 to be replaced by a glutamic acid (E). 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	1.0
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.038
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.24	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.29
Sift	Benign	0.11	T
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.16		Gain of glycosylation at K209 (P = 0.144);
MVP		0.014
MPC		1.8
ClinPred		0.69	D
GERP RS		-7.0
Varity_R		0.085
gMVP		0.37

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: rs200949698; hg19: chr10-81146194;