chr7-48052807-C-A

Variant names:

• chr7-48052807-C-A
• rs776631751
• NM_001100159.3:c.713C>A

Variant summary

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

The NM_001100159.3(C7orf57):​c.713C>A​(p.Thr238Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. T238I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: C7orf57 NM_001100159.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188
• Publications: 0 publications found

Genes affected

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

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=0.08788043).

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.713C>A	p.Thr238Asn	missense	Exon 7 of 9	NP_001093629.1	Q8NEG2-1
	C7orf57	NM_001267865.2		c.299C>A	p.Thr100Asn	missense	Exon 6 of 8	NP_001254794.1	F5H7J8
	C7orf57	NM_001267866.2		c.299C>A	p.Thr100Asn	missense	Exon 6 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.713C>A	p.Thr238Asn	missense	Exon 7 of 9	ENSP00000335500.3	Q8NEG2-1
	C7orf57	ENST00000435376.5	TSL:1	c.299C>A	p.Thr100Asn	missense	Exon 6 of 7	ENSP00000391652.1	Q8NEG2-2
	C7orf57	ENST00000430738.5	TSL:5	c.848C>A	p.Thr283Asn	missense	Exon 7 of 9	ENSP00000410944.1	J3KQX6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249184 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461698 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727130

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111862

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74316

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.19
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.083
Sift	Benign	0.033	D
Sift4G	Benign	0.33	T
Polyphen		0.053	B
Vest4		0.26
MutPred		0.15		Loss of phosphorylation at T238 (P = 0.0093)
MVP		0.076
MPC		0.33
ClinPred		0.25	T
GERP RS		4.6
Varity_R		0.10
gMVP		0.15
Mutation Taster		=93/7	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: rs776631751; hg19: chr7-48092404;