rs190969738

Variant names:

• chr9-37126931-C-A
• rs190969738
• NM_032226.3:c.599C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-37126931-C-A
• chr9-37126931-C-G
• chr9-37126931-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032226.3(ZCCHC7):​c.599C>A​(p.Ser200Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S200F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZCCHC7 NM_032226.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.42
• Publications: 2 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22485062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZCCHC7	NM_032226.3	c.599C>A	p.Ser200Tyr	missense_variant	Exon 2 of 9	ENST00000336755.10	NP_115602.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZCCHC7	ENST00000336755.10	c.599C>A	p.Ser200Tyr	missense_variant	Exon 2 of 9	2	NM_032226.3	ENSP00000337839.5
ZCCHC7	ENST00000534928.5	c.599C>A	p.Ser200Tyr	missense_variant	Exon 2 of 9	1		ENSP00000443113.2
ZCCHC7	ENST00000322831.6	c.596C>A	p.Ser199Tyr	missense_variant	Exon 3 of 4	1		ENSP00000316365.6
ZCCHC7	ENST00000461038.5	n.879C>A		non_coding_transcript_exon_variant	Exon 2 of 9	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461090 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726858

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

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

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5392

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111844

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T;T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	.;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.9	L;L;.
PhyloP100		5.4
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.7	N;.;N
REVEL	Benign	0.21
Sift	Uncertain	0.023	D;.;D
Sift4G	Benign	0.16	T;T;D
Polyphen		0.98	D;D;.
Vest4		0.33
MutPred		0.44		Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);.;
MVP		0.47
MPC		0.40
ClinPred		0.90	D
GERP RS		5.5
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Varity_R		0.12
gMVP		0.54
Mutation Taster		=86/14	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: rs190969738; hg19: chr9-37126928;