dbSNP rs775296113: SERAC1:p.Arg645Leu (chr6-158111397-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032861.4(SERAC1):c.1934G>T(p.Arg645Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SERAC1
NM_032861.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

Variant links:

Genes affected

SERAC1 (HGNC:21061): (serine active site containing 1) The protein encoded by this gene is a phosphatidylglycerol remodeling protein found at the interface of mitochondria and endoplasmic reticula, where it mediates phospholipid exchange. The encoded protein plays a major role in mitochondrial function and intracellular cholesterol trafficking. Defects in this gene are a cause of 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL). Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Aug 2012]

SERAC1 links:

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ACMG classification

Classification made for transcript

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=0.21930501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERAC1	NM_032861.4 link	c.1934G>T	p.Arg645Leu	missense_variant	Exon 17 of 17	ENST00000647468.2	NP_116250.3	Q96JX3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERAC1	ENST00000647468.2 link	c.1934G>T	p.Arg645Leu	missense_variant	Exon 17 of 17		NM_032861.4	ENSP00000496731.1		Q96JX3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241468

Hom.:

AF XY:

0.00000766

AC XY:

AN XY:

130470

show subpopulations

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450868

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721416

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000193

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.087

T;T;.;.;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.87

.;D;D;D;D

M_CAP

Benign

0.080

MetaRNN

Benign

0.22

T;T;T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.33

N;N;.;.;.

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-2.8

D;.;.;.;.

REVEL

Benign

0.24

Sift

Benign

0.31

T;.;.;.;.

Sift4G

Benign

0.30

T;.;.;.;.

Polyphen

0.0

B;B;.;.;.

Vest4

0.12

MutPred

0.45

Loss of solvent accessibility (P = 0.1077);Loss of solvent accessibility (P = 0.1077);.;.;.;

MVP

0.87

MPC

0.32

ClinPred

0.77

GERP RS

4.8

Varity_R

0.15

gMVP

0.59

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over