Variant chr7-48043584-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001100159.3(C7orf57):c.345G>T(p.Gln115His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,612,970 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

C7orf57
NM_001100159.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57

Variant links:

Genes affected

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

C7orf57 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016591787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C7orf57	NM_001100159.3 linkuse as main transcript	c.345G>T	p.Gln115His	missense_variant	4/9	ENST00000348904.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C7orf57	ENST00000348904.4 linkuse as main transcript	c.345G>T	p.Gln115His	missense_variant	4/9	1	NM_001100159.3	P1	Q8NEG2-1

Frequencies

GnomAD3 genomes

AF:

0.000822

AC:

125

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000711

AC:

177

AN:

248888

Hom.:

AF XY:

0.000696

AC XY:

AN XY:

135024

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000557

Gnomad NFE exome

AF:

0.00134

Gnomad OTH exome

AF:

0.000994

GnomAD4 exome

AF:

0.00112

AC:

1642

AN:

1460836

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

795

AN XY:

726762

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000431

Gnomad4 NFE exome

AF:

0.00139

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.000822

AC:

125

AN:

152134

Hom.:

Cov.:

AF XY:

0.000579

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.000590

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.000786

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000260

AC:

ESP6500EA

AF:

0.00108

AC:

ExAC

AF:

0.000769

AC:

EpiCase

AF:

0.00125

EpiControl

AF:

0.00125

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 26, 2023

The c.345G>T (p.Q115H) alteration is located in exon 4 (coding exon 3) of the C7orf57 gene. This alteration results from a G to T substitution at nucleotide position 345, causing the glutamine (Q) at amino acid position 115 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.030

T;.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

0.73

D;N;N;N;N

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.093

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.029

.;.;B

Vest4

0.11

MutPred

0.16

.;.;Gain of glycosylation at T112 (P = 0.1491);

MVP

0.24

MPC

0.16

ClinPred

0.017

GERP RS

3.6

Varity_R

0.084

gMVP

0.27

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over