Variant chr11-17995804-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012139.4(SERGEF):c.614G>C(p.Arg205Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SERGEF
NM_012139.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0910

Variant links:

Genes affected

SERGEF (HGNC:17499): (secretion regulating guanine nucleotide exchange factor) Predicted to enable guanyl-nucleotide exchange factor activity. Involved in negative regulation of protein secretion. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SERGEF links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12910497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SERGEF	NM_012139.4 linkuse as main transcript	c.614G>C	p.Arg205Thr	missense_variant	6/11	ENST00000265965.10	NP_036271.1
SERGEF	NR_104040.2 linkuse as main transcript	n.651G>C		non_coding_transcript_exon_variant	6/12
SERGEF	NR_104041.2 linkuse as main transcript	n.651G>C		non_coding_transcript_exon_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERGEF	ENST00000265965.10 linkuse as main transcript	c.614G>C	p.Arg205Thr	missense_variant	6/11	1	NM_012139.4	ENSP00000265965	P1	Q9UGK8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458518

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725794

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 11, 2023

The c.614G>C (p.R205T) alteration is located in exon 6 (coding exon 6) of the SERGEF gene. This alteration results from a G to C substitution at nucleotide position 614, causing the arginine (R) at amino acid position 205 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.0026

T;.;T;.;T;.;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.71

T;T;T;T;T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.13

T;T;T;T;T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.6

L;L;.;.;.;.;.

MutationTaster

Benign

0.58

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

N;N;N;N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.52

T;T;T;T;T;T;T

Sift4G

Benign

0.51

T;T;T;T;.;.;.

Polyphen

0.0020

B;B;.;B;B;.;.

Vest4

0.22

MutPred

0.46

Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;.;.;.;.;

MVP

0.72

MPC

0.29

ClinPred

0.12

GERP RS

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.069

gMVP

0.44

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over