chr5-133026202-G-A

Variant names:

• chr5-133026202-G-A
• rs3885730
• NM_001300816.3:c.41+295C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001300816.3(ZCCHC10):​c.41+295C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,130 control chromosomes in the GnomAD database, including 4,063 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4063 hom., cov: 31)
• Consequence: ZCCHC10 NM_001300816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 5 publications found

Genes affected

ZCCHC10 (HGNC:25954): (zinc finger CCHC-type containing 10) Predicted to enable nucleic acid binding activity and zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000287054 (HGNC:59144):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300816.3. 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
	ZCCHC10	NM_001300816.3	MANE Select	c.41+295C>T		intron	N/A	NP_001287745.1	Q8TBK6-1
	ZCCHC10	NM_001308127.2		c.41+295C>T		intron	N/A	NP_001295056.1
	ZCCHC10	NM_001300817.3		c.41+295C>T		intron	N/A	NP_001287746.1	B3KVL5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCCHC10	ENST00000509437.6	TSL:1 MANE Select	c.41+295C>T		intron	N/A	ENSP00000423276.1	Q8TBK6-1
	ZCCHC10	ENST00000324170.7	TSL:1	c.41+295C>T		intron	N/A	ENSP00000324274.3	Q8TBK6-2
	ZCCHC10	ENST00000504170.2	TSL:1	c.41+295C>T		intron	N/A	ENSP00000427359.1	D6RIV3

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34517 AN: 152012 Hom.: 4060 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.227 AC: 34544 AN: 152130 Hom.: 4063 Cov.: 31 AF XY: 0.222 AC XY: 16485 AN XY: 74372

African (AFR) AF: 0.235 AC: 9757 AN: 41492

American (AMR) AF: 0.184 AC: 2803 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 830 AN: 3470

East Asian (EAS) AF: 0.101 AC: 525 AN: 5174

South Asian (SAS) AF: 0.164 AC: 791 AN: 4822

European-Finnish (FIN) AF: 0.174 AC: 1846 AN: 10604

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17174 AN: 67990

Other (OTH) AF: 0.253 AC: 532 AN: 2106

Alfa AF: 0.240 Hom.: 8327

Bravo AF: 0.229

Asia WGS AF: 0.119 AC: 414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.8
DANN	Benign	0.94
PhyloP100		-0.20
PromoterAI		-0.045	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3885730;

hg19: chr5-132361894;

COSMIC: COSV60773032;