rs374173126

Variant names:

• chr3-185152819-C-A
• rs374173126
• NM_001025266.3:c.5G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-185152819-C-A
• chr3-185152819-C-G
• chr3-185152819-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001025266.3(C3orf70):​c.5G>T​(p.Ser2Ile) 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. 14/20 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. S2N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C3orf70 NM_001025266.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 1 publications found

Genes affected

C3orf70 (HGNC:33731): (chromosome 3 open reading frame 70) Predicted to be involved in circadian behavior and nervous system development. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3446592).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025266.3. 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
	C3orf70	NM_001025266.3	MANE Select	c.5G>T	p.Ser2Ile	missense	Exon 1 of 2	NP_001020437.1	A6NLC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3orf70	ENST00000335012.3	TSL:1 MANE Select	c.5G>T	p.Ser2Ile	missense	Exon 1 of 2	ENSP00000334974.2	A6NLC5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1396086 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689502

African (AFR) AF: 0.00 AC: 0 AN: 29240

American (AMR) AF: 0.00 AC: 0 AN: 39068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24314

East Asian (EAS) AF: 0.00 AC: 0 AN: 33308

South Asian (SAS) AF: 0.00 AC: 0 AN: 80302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5444

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075340

Other (OTH) AF: 0.00 AC: 0 AN: 57224

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.65
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.33	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.2
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.069
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.19
MutPred		0.33		Gain of stability (P = 0.0068)
MVP		0.030
MPC		0.10
ClinPred		0.14	T
GERP RS		2.5
PromoterAI		0.079	Neutral
Varity_R		0.20
gMVP		0.40
Mutation Taster		=76/24	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: rs374173126; hg19: chr3-184870607;