rs1565798439

Variant names:

• chr12-71610513-A-G
• rs1565798439
• NM_144982.5:c.5885T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_144982.5(ZFC3H1):​c.5885T>C​(p.Leu1962Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFC3H1 NM_144982.5 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.15
• Publications: 0 publications found

Genes affected

ZFC3H1 (HGNC:28328): (zinc finger C3H1-type containing) Predicted to enable metal ion binding activity. Predicted to be involved in RNA processing. Located in nucleus. Part of exosome (RNase complex). [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
• PP5: Variant 12-71610513-A-G is Pathogenic according to our data. Variant chr12-71610513-A-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 599528.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144982.5. 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
	ZFC3H1	NM_144982.5	MANE Select	c.5885T>C	p.Leu1962Pro	missense	Exon 35 of 35	NP_659419.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFC3H1	ENST00000378743.9	TSL:1 MANE Select	c.5885T>C	p.Leu1962Pro	missense	Exon 35 of 35	ENSP00000368017.4	O60293-1
	ZFC3H1	ENST00000552994.5	TSL:1	n.*840T>C		non_coding_transcript_exon	Exon 34 of 34	ENSP00000446995.1	O60293-2
	ZFC3H1	ENST00000552994.5	TSL:1	n.*840T>C		3_prime_UTR	Exon 34 of 34	ENSP00000446995.1	O60293-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Short stature (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.81	L
PhyloP100		7.1
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.61		Loss of helix (P = 3e-04)
MVP		0.16
MPC		1.4
ClinPred		0.82	D
GERP RS		5.7
Varity_R		0.63
gMVP		0.91
Mutation Taster		=35/65	disease causing (ClinVar)

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: rs1565798439; hg19: chr12-72004293;