1-207022046-G-T

Variant names:

• chr1-207022046-G-T
• rs141737723
• NM_023938.6:c.1718C>A

Variant summary

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

The NM_023938.6(C1orf116):​c.1718C>A​(p.Pro573His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,450,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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. P573R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: C1orf116 NM_023938.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 0 publications found

Genes affected

C1orf116 (HGNC:28667): (chromosome 1 open reading frame 116) Located in cytosol and plasma membrane. [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=0.1437701).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023938.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf116	NM_023938.6	MANE Select	c.1718C>A	p.Pro573His	missense	Exon 4 of 4	NP_076427.2
	C1orf116	NM_001083924.2		c.980C>A	p.Pro327His	missense	Exon 3 of 3	NP_001077393.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf116	ENST00000359470.6	TSL:1 MANE Select	c.1718C>A	p.Pro573His	missense	Exon 4 of 4	ENSP00000352447.5	Q9BW04-1
	C1orf116	ENST00000895722.1		c.1718C>A	p.Pro573His	missense	Exon 4 of 4	ENSP00000565781.1
	C1orf116	ENST00000938289.1		c.1718C>A	p.Pro573His	missense	Exon 4 of 4	ENSP00000608348.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000292 AC: 7 AN: 239372 AF XY: 0.00000776

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000368

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000200 AC: 29 AN: 1450446 Hom.: 0 Cov.: 29 AF XY: 0.0000208 AC XY: 15 AN XY: 720740

African (AFR) AF: 0.0000303 AC: 1 AN: 33040

American (AMR) AF: 0.00 AC: 0 AN: 43344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39658

South Asian (SAS) AF: 0.0000477 AC: 4 AN: 83938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52832

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5710

European-Non Finnish (NFE) AF: 0.0000163 AC: 18 AN: 1106842

Other (OTH) AF: 0.00 AC: 0 AN: 59912

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000529 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.4
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.058
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0020	D
Vest4		0.076
MVP		0.15
MPC		0.092
ClinPred		0.37	T
GERP RS		2.2
gMVP		0.064
Mutation Taster		=82/18	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: rs141737723; hg19: chr1-207195391;