1-11788023-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001010881(C1orf167):c.3824G>A(p.Ser1275Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 152232 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

C1orf167
NM_001010881 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

Links

C1orf167 (HGNC:25262):

MTHFR (HGNC:7436):

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053456426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1orf167	NM_001010881.2 linkuse as main transcript	c.3824G>A	p.Ser1275Asn	missense_variant	18/21	ENST00000688073.1
MTHFR	NM_005957.5 linkuse as main transcript	c.*2657C>T		3_prime_UTR_variant	12/12	ENST00000376590.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1orf167	ENST00000688073.1 linkuse as main transcript	c.3824G>A	p.Ser1275Asn	missense_variant	18/21		NM_001010881.2	A2
MTHFR	ENST00000376590.9 linkuse as main transcript	c.*2657C>T		3_prime_UTR_variant	12/12	1	NM_005957.5	A1	P42898-1

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

182

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00207

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00125

AC:

185

AN:

147914

Hom.:

AF XY:

0.00119

AC XY:

AN XY:

79538

show subpopulations

Gnomad AFR exome

AF:

0.000447

Gnomad AMR exome

AF:

0.000294

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000996

Gnomad FIN exome

AF:

0.00175

Gnomad NFE exome

AF:

0.00184

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.00135

AC:

1551

AN:

1148882

Hom.:

AF XY:

0.00135

AC XY:

763

AN XY:

563252

show subpopulations

Gnomad4 AFR exome

AF:

0.000206

Gnomad4 AMR exome

AF:

0.000253

Gnomad4 ASJ exome

AF:

0.00179

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.00165

Gnomad4 NFE exome

AF:

0.00143

Gnomad4 OTH exome

AF:

0.00133

Alfa

AF:

0.00155

Hom.:

Bravo

AF:

0.00110

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.00118

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Homocystinuria due to methylene tetrahydrofolate reductase deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Jun 11, 2018

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

Cadd

Benign

Dann

Benign

0.87

DEOGEN2

Benign

0.0018

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.36

M_CAP

Benign

0.031

MetaRNN

Benign

0.0053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Benign

-0.94

REVEL

Benign

0.071

Sift

Pathogenic

0.0

Sift4G

Benign

0.14

Polyphen

0.57

Vest4

0.044

MVP

0.067

MPC

0.55

ClinPred

0.027

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.078

Splicing

Find out SpliceAI 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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over