rs1478891202

Variant names:

• chr1-173952095-T-A
• rs1478891202
• NM_172071.4:c.2414A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-173952095-T-A
• chr1-173952095-T-C

Variant summary

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

The NM_172071.4(RC3H1):​c.2414A>T​(p.Asn805Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,445,772 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N805S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RC3H1 NM_172071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.15
• Publications: 0 publications found

Genes affected

RC3H1 (HGNC:29434): (ring finger and CCCH-type domains 1) This gene encodes a protein containing RING-type and C3H1-type zinc finger motifs. The encoded protein recognizes and binds to a constitutive decay element (CDE) in the 3' UTR of mRNAs, leading to mRNA deadenylation and degradation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

RC3H1 Gene-Disease associations (from GenCC):

• hemophagocytic lymphohistiocytosis, familial, 6

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RC3H1	NM_172071.4	c.2414A>T	p.Asn805Ile	missense_variant	Exon 14 of 20	ENST00000367696.7	NP_742068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RC3H1	ENST00000367696.7	c.2414A>T	p.Asn805Ile	missense_variant	Exon 14 of 20	5	NM_172071.4	ENSP00000356669.2
RC3H1	ENST00000367694.2	c.2414A>T	p.Asn805Ile	missense_variant	Exon 13 of 19	2		ENSP00000356667.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445772 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718914

African (AFR) AF: 0.00 AC: 0 AN: 33036

American (AMR) AF: 0.00 AC: 0 AN: 43454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25678

East Asian (EAS) AF: 0.00 AC: 0 AN: 39222

South Asian (SAS) AF: 0.00 AC: 0 AN: 82858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103346

Other (OTH) AF: 0.00 AC: 0 AN: 59580

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T;T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;.;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L;L;L
PhyloP100		6.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Benign	0.29
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.035	D;D;D
Polyphen		0.89	P;P;P
Vest4		0.55
MutPred		0.70		Loss of disorder (P = 0.0435);Loss of disorder (P = 0.0435);Loss of disorder (P = 0.0435);
MVP		0.26
MPC		0.79
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.48
gMVP		0.35
Mutation Taster		=88/12	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: rs1478891202; hg19: chr1-173921233;