Genetic Variant NM_019095.6:c.85C>A (chr20-6006331-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019095.6(CRLS1):c.85C>A(p.Arg29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,200,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

CRLS1
NM_019095.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0920

Publications

0 publications found

Variant links:

Genes affected

CRLS1 (HGNC:16148): (cardiolipin synthase 1) This gene encodes a member of the CDP-alcohol phosphatidyltransferase class-I family of proteins. The encoded enzyme catalyzes the synthesis of cardiolipin, a phospholipid component of mitochondrial membranes that is critical for mitochondrial function. [provided by RefSeq, Apr 2016]

CRLS1 links:

ENSG00000286235 (HGNC:):

ENSG00000286235 links:

MCM8-AS1 (HGNC:51230): (MCM8 antisense RNA 1)

MCM8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06025991).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019095.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRLS1	NM_019095.6	MANE Select	c.85C>A	p.Arg29Ser	missense	Exon 1 of 7	NP_061968.1	Q9UJA2-1
CRLS1	NM_001323563.2		c.-311C>A		5_prime_UTR	Exon 1 of 7	NP_001310492.1
CRLS1	NM_001323562.2		c.-28+220C>A		intron	N/A	NP_001310491.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRLS1	ENST00000378863.9	TSL:1 MANE Select	c.85C>A	p.Arg29Ser	missense	Exon 1 of 7	ENSP00000368140.4	Q9UJA2-1
CRLS1	ENST00000452938.5	TSL:1	c.85C>A	p.Arg29Ser	missense	Exon 1 of 6	ENSP00000416770.1	Q6NTG3
ENSG00000286235	ENST00000652720.1		c.2431-3444C>A		intron	N/A	ENSP00000498784.1	A0A494C100

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000191

AC:

AN:

52452

AF XY:

0.0000322

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000416

AC:

AN:

1200834

Hom.:

Cov.:

AF XY:

0.00000683

AC XY:

AN XY:

586016

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24830

American (AMR)

AF:

0.00

AC:

AN:

18244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19340

East Asian (EAS)

AF:

0.00

AC:

AN:

26440

South Asian (SAS)

AF:

0.000101

AC:

AN:

49534

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27674

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3430

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

982896

Other (OTH)

AF:

0.00

AC:

AN:

48446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.2

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.023

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.48

M_CAP

Benign

0.016

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

PhyloP100

0.092

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.74

REVEL

Benign

0.015

Sift

Benign

0.18

Sift4G

Benign

0.30

Polyphen

0.0020

Vest4

0.070

MutPred

0.24

Gain of glycosylation at R29 (P = 0.0322)

MVP

0.10

MPC

0.13

ClinPred

0.037

GERP RS

-0.62

PromoterAI

-0.054

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.11

gMVP

0.41

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over