15-43793946-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001199875.1(SERF2):c.487C>A(p.Leu163Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,552,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

SERF2
NM_001199875.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

Variant links:

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]

SERF2 links:

ENSG00000262560 (HGNC:):

ENSG00000262560 links:

SERINC4 (HGNC:32237): (serine incorporator 4) Predicted to be involved in phospholipid biosynthetic process. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

SERINC4 links:

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]

MIR1282 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33969373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERF2	NM_001018108.4 link	c.*173C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000249786.9	NP_001018118.1	P84101-1
SERINC4	NM_001258031.2 link	c.*1054G>T		downstream_gene_variant		ENST00000319327.7	NP_001244960.1	A6NH21-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERF2	ENST00000249786.9 link	c.*173C>A	3_prime_UTR_variant	Exon 3 of 3	1	NM_001018108.4	ENSP00000249786.4	P84101-1
ENSG00000262560	ENST00000417761.2 link	n.*439+1442G>T	intron_variant	Intron 7 of 16	2		ENSP00000415219.2	H7C423
SERINC4	ENST00000319327.7 link	c.*1054G>T	downstream_gene_variant		5	NM_001258031.2	ENSP00000319796.6	A6NH21-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000126

AC:

AN:

158242

Hom.:

AF XY:

0.0000119

AC XY:

AN XY:

84116

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000402

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000162

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000500

AC:

AN:

1400304

Hom.:

Cov.:

AF XY:

0.00000579

AC XY:

AN XY:

691308

show subpopulations

Gnomad4 AFR exome

AF:

0.000126

Gnomad4 AMR exome

AF:

0.0000279

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000344

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000194

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.487C>A (p.L163I) alteration is located in exon 3 (coding exon 3) of the SERF2 gene. This alteration results from a C to A substitution at nucleotide position 487, causing the leucine (L) at amino acid position 163 to be replaced by an isoleucine (I). 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

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.98

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.71

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.32

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.037

D;D

Vest4

0.43

MutPred

0.14

Gain of sheet (P = 0.039);.;

MVP

0.72

MPC

0.15

ClinPred

0.40

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over