11-17988609-C-G

Position:

• chr11-17988609-C-G

Variant summary

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

The NM_012139.4(SERGEF):​c.832G>C​(p.Val278Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SERGEF NM_012139.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERGEF	NM_012139.4	c.832G>C	p.Val278Leu	missense_variant	8/11	ENST00000265965.10	NP_036271.1
SERGEF	NR_104040.2	n.869G>C		non_coding_transcript_exon_variant	8/12
SERGEF	NR_104041.2	n.869G>C		non_coding_transcript_exon_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERGEF	ENST00000265965.10	c.832G>C	p.Val278Leu	missense_variant	8/11	1	NM_012139.4	ENSP00000265965	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Dec 07, 2023

The c.832G>C (p.V278L) alteration is located in exon 8 (coding exon 8) of the SERGEF gene. This alteration results from a G to C substitution at nucleotide position 832, causing the valine (V) at amino acid position 278 to be replaced by a leucine (L). 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	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0038	T;.;.;T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.77	T;T;T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.39	T;T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.2	M;M;.;.;.
MutationTaster	Benign	0.90	D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.0	N;N;N;N;N
REVEL	Uncertain	0.45
Sift	Benign	0.17	T;T;T;T;T
Sift4G	Benign	0.36	T;T;D;.;.
Polyphen		0.61	P;P;B;D;.
Vest4		0.52
MutPred		0.55		Loss of catalytic residue at Q280 (P = 0.1196);Loss of catalytic residue at Q280 (P = 0.1196);.;.;.;
MVP		0.65
MPC		0.22
ClinPred		0.57	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.068
gMVP		0.56

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: chr11-18010156;