9-37349421-A-G

Variant names:

• chr9-37349421-A-G
• rs779726986
• NM_032226.3:c.1052A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032226.3(ZCCHC7):​c.1052A>G​(p.Tyr351Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,034 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: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ZCCHC7 NM_032226.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.826

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032226.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCCHC7	NM_032226.3	MANE Select	c.1052A>G	p.Tyr351Cys	missense	Exon 7 of 9	NP_115602.2	Q8N3Z6-1
	ZCCHC7	NM_001289119.2		c.1052A>G	p.Tyr351Cys	missense	Exon 7 of 9	NP_001276048.1	Q8N3Z6-1
	ZCCHC7	NM_001289120.2		c.1052A>G	p.Tyr351Cys	missense	Exon 7 of 9	NP_001276049.1	Q8N3Z6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCCHC7	ENST00000336755.10	TSL:2 MANE Select	c.1052A>G	p.Tyr351Cys	missense	Exon 7 of 9	ENSP00000337839.5	Q8N3Z6-1
	ZCCHC7	ENST00000534928.5	TSL:1	c.1052A>G	p.Tyr351Cys	missense	Exon 7 of 9	ENSP00000443113.2	Q8N3Z6-1
	ZCCHC7	ENST00000461038.5	TSL:1	n.1332A>G		non_coding_transcript_exon	Exon 7 of 9

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251296 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461812 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727200

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111964

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74376

African (AFR) AF: 0.0000482 AC: 2 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000708 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.62
Sift	Benign	0.17	T
Sift4G	Benign	0.14	T
Polyphen		0.89	P
Vest4		0.90
MutPred		0.63		Loss of sheet (P = 0.0084)
MVP		0.82
MPC		0.58
ClinPred		0.20	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.058
gMVP		0.82
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

dbSNP: rs779726986; hg19: chr9-37349418;