rs945797576

Variant names:

• chr1-162379016-C-A
• rs945797576
• ENST00000420220.1:c.-11-2875C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-162379016-C-A
• chr1-162379016-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135240.3(C1orf226):​c.103C>A​(p.Pro35Thr) 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. 11/16 in silico tools predict a benign outcome for this variant. 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. P35S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C1orf226 NM_001135240.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

Genes affected

ENSG00000254706 (HGNC:):

C1orf226 (HGNC:34351): (chromosome 1 open reading frame 226)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11469343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf226	NM_001135240.3	c.103C>A	p.Pro35Thr	missense_variant	Exon 1 of 3		NP_001128712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000254706	ENST00000420220.1	c.-11-2875C>A		intron_variant	Intron 2 of 3	5		ENSP00000398035.1
C1orf226	ENST00000426197.2	c.103C>A	p.Pro35Thr	missense_variant	Exon 1 of 3	2		ENSP00000413150.2
ENSG00000254706	ENST00000431696.1	c.227-2875C>A		intron_variant	Intron 2 of 2	4		ENSP00000405676.2
ENSG00000254706	ENST00000367932.3	n.153-2875C>A		intron_variant	Intron 1 of 2	4		ENSP00000356909.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1396676 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 689106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.98
Eigen	Benign	0.15
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.86	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.075
Sift	Benign	0.098	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.60	P
Vest4		0.25
MutPred		0.084		Gain of phosphorylation at P35 (P = 0.0762);
MVP		0.043
MPC		0.073
ClinPred		0.62	D
GERP RS		4.7
gMVP		0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs945797576; hg19: chr1-162348806;