NM_203303.3:c.278C>G

Variant names:

• chrX-74304544-C-G
• rs775392658
• NM_203303.3:c.278C>G

Variant summary

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

The NM_203303.3(ZCCHC13):​c.278C>G​(p.Thr93Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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. T93N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZCCHC13 NM_203303.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310
• 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: 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=0.16923898).

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.278C>G	p.Thr93Ser	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.278C>G	p.Thr93Ser	missense	Exon 1 of 1	ENSP00000345633.2	Q8WW36

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.040
DANN	Benign	0.50
DEOGEN2	Benign	0.0024	T
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.54	N
PhyloP100		0.31
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.019
Sift	Benign	0.42	T
Sift4G	Benign	0.43	T
Polyphen		0.0060	B
Vest4		0.14
MutPred		0.37		Gain of disorder (P = 0.079)
MVP		0.030
MPC		0.34
ClinPred		0.053	T
GERP RS		-3.4
PromoterAI		0.033	Neutral
Varity_R		0.031
gMVP		0.23
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs775392658; hg19: chrX-73524379;