chr15-43793767-C-G

Variant names:

• chr15-43793767-C-G
• rs747940819
• ENST00000409960.6:c.308C>G

Variant summary

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

The NM_001199875.1(SERF2):​c.308C>G​(p.Pro103Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,882 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (1 hom.)
• Consequence: SERF2 NM_001199875.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40

Genes affected

SERF2 (HGNC:10757): (small EDRK-rich factor 2) Involved in protein destabilization. Predicted to be located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000262560 (HGNC:):

MIR1282 (HGNC:35360): (microRNA 1282) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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 rank	MANE	Protein	UniProt
SERF2	NM_001018108.4	c.174C>G	p.Pro58Pro	synonymous_variant	Exon 3 of 3	ENST00000249786.9	NP_001018118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERF2	ENST00000249786.9	c.174C>G	p.Pro58Pro	synonymous_variant	Exon 3 of 3	1	NM_001018108.4	ENSP00000249786.4
ENSG00000262560	ENST00000417761.2	n.*439+1621G>C		intron_variant	Intron 7 of 16	2		ENSP00000415219.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251452 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135900

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461882 Hom.: 1 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727244

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: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	11
DANN	Uncertain	1.0
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Uncertain	-0.22	T
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.095	T;T
Vest4		0.66
MutPred		0.19		Loss of glycosylation at P103 (P = 0.0063);.;
MVP		0.64
MPC		0.30
ClinPred		0.64	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs747940819; hg19: chr15-44085965;