rs2708912

Positions:

• chr7-48046480-C-A
• chr7-48046480-C-G
• chr7-48046480-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C7orf57	NM_001100159.3	c.371C>A	p.Pro124Gln	missense_variant	5/9	ENST00000348904.4	NP_001093629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C7orf57	ENST00000348904.4	c.371C>A	p.Pro124Gln	missense_variant	5/9	1	NM_001100159.3	ENSP00000335500	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;.;.;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.81	T;T;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.84	D;D;D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.7	.;.;.;.;M
MutationTaster	Benign	0.0000085	P;P;P;P;P
PROVEAN	Pathogenic	-6.4	D;.;D;D;D
REVEL	Uncertain	0.29
Sift	Benign	0.039	D;.;D;T;D
Sift4G	Uncertain	0.0040	D;D;D;D;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2708912; hg19: chr7-48086077;