rs211146

Positions:

• chr11-17959500-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012139.4(SERGEF):​c.981G>A​(p.Ser327=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,612,984 control chromosomes in the GnomAD database, including 305,832 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (35541 hom., cov: 31)
  • Exomes 𝑓: 0.60 (270291 hom.)
• Consequence: SERGEF NM_012139.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-3.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERGEF	NM_012139.4	c.981G>A	p.Ser327=	synonymous_variant	9/11	ENST00000265965.10	NP_036271.1
SERGEF	NR_104040.2	n.1018G>A		non_coding_transcript_exon_variant	9/12
SERGEF	NR_104041.2	n.881+29097G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERGEF	ENST00000265965.10	c.981G>A	p.Ser327=	synonymous_variant	9/11	1	NM_012139.4	ENSP00000265965	P1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 102012 AN: 151926 Hom.: 35492 Cov.: 31

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.651

GnomAD3 exomes AF: 0.601 AC: 150615 AN: 250788 Hom.: 46278 AF XY: 0.601 AC XY: 81414 AN XY: 135512

Gnomad AFR exome AF: 0.880

Gnomad AMR exome AF: 0.543

Gnomad ASJ exome AF: 0.481

Gnomad EAS exome AF: 0.494

Gnomad SAS exome AF: 0.661

Gnomad FIN exome AF: 0.552

Gnomad NFE exome AF: 0.600

Gnomad OTH exome AF: 0.590

GnomAD4 exome AF: 0.605 AC: 883764 AN: 1460940 Hom.: 270291 Cov.: 42 AF XY: 0.606 AC XY: 440111 AN XY: 726828

Gnomad4 AFR exome AF: 0.879

Gnomad4 AMR exome AF: 0.546

Gnomad4 ASJ exome AF: 0.480

Gnomad4 EAS exome AF: 0.470

Gnomad4 SAS exome AF: 0.654

Gnomad4 FIN exome AF: 0.554

Gnomad4 NFE exome AF: 0.605

Gnomad4 OTH exome AF: 0.610

GnomAD4 genome AF: 0.672 AC: 102123 AN: 152044 Hom.: 35541 Cov.: 31 AF XY: 0.666 AC XY: 49492 AN XY: 74306

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.655

Alfa AF: 0.611 Hom.: 46196

Bravo AF: 0.679

Asia WGS AF: 0.626 AC: 2179 AN: 3478

EpiCase AF: 0.608

EpiControl AF: 0.593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.16
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs211146; hg19: chr11-17981047; COSMIC: COSV56382104;