9-37305593-C-T

Variant names:

• chr9-37305593-C-T
• NM_032226.3:c.830C>T

Variant summary

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

The NM_032226.3(ZCCHC7):​c.830C>T​(p.Ser277Phe) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZCCHC7 NM_032226.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.376

Genes affected

ZCCHC7 (HGNC:26209): (zinc finger CCHC-type containing 7) Enables RNA binding activity. Located in cytosol and nucleolus. [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=0.1496428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZCCHC7	NM_032226.3	c.830C>T	p.Ser277Phe	missense_variant	Exon 5 of 9	ENST00000336755.10	NP_115602.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZCCHC7	ENST00000336755.10	c.830C>T	p.Ser277Phe	missense_variant	Exon 5 of 9	2	NM_032226.3	ENSP00000337839.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.830C>T (p.S277F) alteration is located in exon 5 (coding exon 4) of the ZCCHC7 gene. This alteration results from a C to T substitution at nucleotide position 830, causing the serine (S) at amino acid position 277 to be replaced by a phenylalanine (F). 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	Benign	0.25
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.8	D;.
REVEL	Benign	0.070
Sift	Benign	0.095	T;.
Sift4G	Uncertain	0.017	D;D
Polyphen		0.0010	B;B
Vest4		0.27
MutPred		0.42		Loss of disorder (P = 0.0224);Loss of disorder (P = 0.0224);
MVP		0.040
MPC		0.19
ClinPred		0.16	T
GERP RS		2.1
Varity_R		0.076
gMVP		0.47

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: chr9-37305590;