chr1-28529898-C-T

Variant names:

• chr1-28529898-C-T
• rs1664007505
• NM_001381865.2:c.32C>T

Variant summary

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

The NM_001381865.2(RCC1):​c.32C>T​(p.Ser11Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RCC1 NM_001381865.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.51
• Publications: 0 publications found

Genes affected

RCC1 (HGNC:1913): (regulator of chromosome condensation 1) Enables several functions, including guanyl-nucleotide exchange factor activity; nucleosomal DNA binding activity; and protein heterodimerization activity. Involved in several processes, including G1/S transition of mitotic cell cycle; regulation of mitotic nuclear division; and spindle organization. Located in chromatin; cytoplasm; and nucleus. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.23002121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCC1	NM_001381865.2	c.32C>T	p.Ser11Phe	missense_variant	Exon 5 of 13	ENST00000683442.1	NP_001368794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCC1	ENST00000683442.1	c.32C>T	p.Ser11Phe	missense_variant	Exon 5 of 13		NM_001381865.2	ENSP00000508074.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151992 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461322 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726972

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111598

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151992 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74248

African (AFR) AF: 0.0000242 AC: 1 AN: 41362

American (AMR) AF: 0.00 AC: 0 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.32C>T (p.S11F) alteration is located in exon 2 (coding exon 1) of the RCC1 gene. This alteration results from a C to T substitution at nucleotide position 32, causing the serine (S) at amino acid position 11 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.0020	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.;T;.;T;T;T;.;.;T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.89	D;.;D;D;.;D;.;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.34	N;N;.;.;N;.;N;N;.;.;.
PhyloP100		2.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.6	D;.;D;.;D;D;D;N;N;.;D
REVEL	Benign	0.12
Sift	Uncertain	0.025	D;.;D;.;D;D;D;D;D;.;D
Sift4G	Uncertain	0.060	T;.;D;.;T;D;T;T;T;D;D
Polyphen		0.83	P;D;.;.;P;.;P;D;.;.;.
Vest4		0.36
MutPred		0.32		Loss of phosphorylation at S11 (P = 0.0014);Loss of phosphorylation at S11 (P = 0.0014);Loss of phosphorylation at S11 (P = 0.0014);Loss of phosphorylation at S11 (P = 0.0014);Loss of phosphorylation at S11 (P = 0.0014);Loss of phosphorylation at S11 (P = 0.0014);Loss of phosphorylation at S11 (P = 0.0014);Loss of phosphorylation at S11 (P = 0.0014);Loss of phosphorylation at S11 (P = 0.0014);.;Loss of phosphorylation at S11 (P = 0.0014);
MVP		0.57
MPC		1.2
ClinPred		0.92	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.22
Mutation Taster		=64/36	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: rs1664007505; hg19: chr1-28856410;