9-37126439-A-C

Variant names:

• chr9-37126439-A-C
• rs139862637
• NM_032226.3:c.107A>C

Variant summary

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

The NM_032226.3(ZCCHC7):​c.107A>C​(p.Tyr36Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. Y36C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZCCHC7 NM_032226.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.33
• 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, 0.771

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.107A>C	p.Tyr36Ser	missense	Exon 2 of 9	NP_115602.2	Q8N3Z6-1
	ZCCHC7	NM_001289119.2		c.107A>C	p.Tyr36Ser	missense	Exon 2 of 9	NP_001276048.1	Q8N3Z6-1
	ZCCHC7	NM_001289120.2		c.107A>C	p.Tyr36Ser	missense	Exon 2 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.107A>C	p.Tyr36Ser	missense	Exon 2 of 9	ENSP00000337839.5	Q8N3Z6-1
	ZCCHC7	ENST00000534928.5	TSL:1	c.107A>C	p.Tyr36Ser	missense	Exon 2 of 9	ENSP00000443113.2	Q8N3Z6-1
	ZCCHC7	ENST00000322831.6	TSL:1	c.104A>C	p.Tyr35Ser	missense	Exon 3 of 4	ENSP00000316365.6	X6R4A7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461606 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727106

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5574

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	-0.098	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.3
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.76
MutPred		0.37		Gain of disorder (P = 0.0293)
MVP		0.48
MPC		0.52
ClinPred		0.93	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.55
gMVP		0.43
Mutation Taster		=76/24	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: rs139862637; hg19: chr9-37126436;