1-172468452-G-T

Variant names:

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

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>T​(p.Ser137Ile) 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. 13/21 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: not found (cov: 32)
• 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=0.23810962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf105	NM_139240.4	c.410G>T	p.Ser137Ile	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>T	p.Ser137Ile	missense_variant	Exon 7 of 7	1	NM_139240.4	ENSP00000356700.4
C1orf105	ENST00000367725.4	c.380G>T	p.Ser127Ile	missense_variant	Exon 5 of 5	2		ENSP00000356698.4
C1orf105	ENST00000367726.1	n.214G>T		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.031	T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.
PhyloP100		-0.31
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.99	D;.
Vest4		0.37
MutPred		0.30		Loss of disorder (P = 0.0213);.;
MVP		0.40
MPC		0.16
ClinPred		0.95	D
GERP RS		1.1
Varity_R		0.40
gMVP		0.092
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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;