1-172468452-G-C

Variant names:

• chr1-172468452-G-C
• rs1129942
• NM_139240.4:c.410G>C

Variant summary

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

The NM_139240.4(C1orf105):​c.410G>C​(p.Ser137Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: C1orf105 NM_139240.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• Publications: 27 publications found

Genes affected

C1orf105 (HGNC:29591): (chromosome 1 open reading frame 105)

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=0.13399985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf105	NM_139240.4	c.410G>C	p.Ser137Thr	missense_variant	Exon 7 of 7	ENST00000367727.9	NP_640333.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1orf105	ENST00000367727.9	c.410G>C	p.Ser137Thr	missense_variant	Exon 7 of 7	1	NM_139240.4	ENSP00000356700.4
C1orf105	ENST00000367725.4	c.380G>C	p.Ser127Thr	missense_variant	Exon 5 of 5	2		ENSP00000356698.4
C1orf105	ENST00000367726.1	n.214G>C		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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 Cov.: 37

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152062 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74278

African (AFR) AF: 0.00 AC: 0 AN: 41370

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.2
DANN	Benign	0.93
DEOGEN2	Benign	0.021	T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.
PhyloP100		-0.31
PROVEAN	Uncertain	-2.4	N;D
REVEL	Benign	0.11
Sift	Benign	0.033	D;D
Sift4G	Uncertain	0.044	D;D
Polyphen		0.93	P;.
Vest4		0.26
MutPred		0.19		Gain of sheet (P = 0.0344);.;
MVP		0.26
MPC		0.11
ClinPred		0.68	D
GERP RS		1.1
Varity_R		0.092
gMVP		0.027
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1129942; hg19: chr1-172437592;