7-48046480-C-A

Variant names:

• chr7-48046480-C-A
• rs2708912
• NM_001100159.3:c.371C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001100159.3(C7orf57):​c.371C>A​(p.Pro124Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: C7orf57 NM_001100159.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.91
• Publications: 26 publications found

Genes affected

C7orf57 (HGNC:22247): (chromosome 7 open reading frame 57)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.844

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100159.3. 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
	C7orf57	NM_001100159.3	MANE Select	c.371C>A	p.Pro124Gln	missense	Exon 5 of 9	NP_001093629.1	Q8NEG2-1
	C7orf57	NM_001267865.2		c.5C>A	p.Pro2Gln	missense	Exon 4 of 8	NP_001254794.1	F5H7J8
	C7orf57	NM_001267866.2		c.5C>A	p.Pro2Gln	missense	Exon 4 of 7	NP_001254795.1	Q8NEG2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7orf57	ENST00000348904.4	TSL:1 MANE Select	c.371C>A	p.Pro124Gln	missense	Exon 5 of 9	ENSP00000335500.3	Q8NEG2-1
	C7orf57	ENST00000435376.5	TSL:1	c.5C>A	p.Pro2Gln	missense	Exon 4 of 7	ENSP00000391652.1	Q8NEG2-2
	C7orf57	ENST00000430738.5	TSL:5	c.506C>A	p.Pro169Gln	missense	Exon 5 of 9	ENSP00000410944.1	J3KQX6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.9
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.29
Sift	Benign	0.039	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.34		Loss of phosphorylation at S122 (P = 0.1395)
MVP		0.48
MPC		0.62
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.56
gMVP		0.55
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2708912; hg19: chr7-48086077;