11-17995806-G-C

Position:

• chr11-17995806-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012139.4(SERGEF):​c.612C>G​(p.Ser204Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: SERGEF NM_012139.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.747

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]

ACMG classification

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=0.24642396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERGEF	NM_012139.4	c.612C>G	p.Ser204Arg	missense_variant	6/11	ENST00000265965.10	NP_036271.1
SERGEF	NR_104040.2	n.649C>G		non_coding_transcript_exon_variant	6/12
SERGEF	NR_104041.2	n.649C>G		non_coding_transcript_exon_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERGEF	ENST00000265965.10	c.612C>G	p.Ser204Arg	missense_variant	6/11	1	NM_012139.4	ENSP00000265965	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2023

The c.612C>G (p.S204R) alteration is located in exon 6 (coding exon 6) of the SERGEF gene. This alteration results from a C to G substitution at nucleotide position 612, causing the serine (S) at amino acid position 204 to be replaced by an arginine (R). 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	0.23
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0050	T;.;T;.;T;.;T
Eigen	Benign	-0.025
Eigen_PC	Benign	0.046
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.87	D;D;D;D;D;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.25	T;T;T;T;T;T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.6	L;L;.;.;.;.;.
MutationTaster	Benign	0.93	D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.24	T;T;T;T;T;T;T
Sift4G	Benign	0.56	T;T;T;T;.;.;.
Polyphen		0.87	P;P;.;P;P;.;.
Vest4		0.35
MutPred		0.30		Loss of ubiquitination at K201 (P = 0.0496);Loss of ubiquitination at K201 (P = 0.0496);.;.;.;.;.;
MVP		0.77
MPC		0.23
ClinPred		0.81	D
GERP RS		3.8
Varity_R		0.18
gMVP		0.64

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.

Other links and lift over

hg19: chr11-18017353;