rs759508253

Variant names:

• chrX-74304513-C-A
• rs759508253
• NM_203303.3:c.247C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-74304513-C-A
• chrX-74304513-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_203303.3(ZCCHC13):​c.247C>A​(p.Pro83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,210,830 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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. P83S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000064 (0 hom. 1 hem.)
• Consequence: ZCCHC13 NM_203303.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56
• Publications: 0 publications found

Genes affected

ZCCHC13 (HGNC:31749): (zinc finger CCHC-type containing 13) This gene appears to represent an intronless retrocopy of a related multi-exon gene located on chromosome 3. However, the CDS of this intronless gene remains relatively intact, it is conserved in other mammalian species, it is known to be transcribed, and it is therefore thought to encode a functional protein. The encoded protein contains six CCHC-type zinc fingers, and is thus thought to function as a transcription factor. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049046338).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203303.3. 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
	ZCCHC13	NM_203303.3	MANE Select	c.247C>A	p.Pro83Thr	missense	Exon 1 of 1	NP_976048.1	Q8WW36

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCCHC13	ENST00000339534.4	TSL:6 MANE Select	c.247C>A	p.Pro83Thr	missense	Exon 1 of 1	ENSP00000345633.2	Q8WW36

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112567 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000560

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: 0.0000272 AC: 5 AN: 183492 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000361

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000637 AC: 7 AN: 1098263 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1 AN XY: 363617

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.000199 AC: 6 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842144

Other (OTH) AF: 0.00 AC: 0 AN: 46098

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112567 Hom.: 0 Cov.: 23 AF XY: 0.0000288 AC XY: 1 AN XY: 34713

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31005

American (AMR) AF: 0.00 AC: 0 AN: 10680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2659

East Asian (EAS) AF: 0.000560 AC: 2 AN: 3571

South Asian (SAS) AF: 0.00 AC: 0 AN: 2708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6197

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53309

Other (OTH) AF: 0.00 AC: 0 AN: 1516

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.6
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.078
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.047	D
Polyphen		0.24	B
Vest4		0.096
MutPred		0.37		Gain of phosphorylation at P83 (P = 0.0364)
MVP		0.055
MPC		0.60
ClinPred		0.25	T
GERP RS		2.5
PromoterAI		-0.031	Neutral
Varity_R		0.28
gMVP		0.35
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs759508253; hg19: chrX-73524348;