Genetic Variant NM_198469.4:c.-2C>T (chr9-122159971-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_198469.4(MORN5):c.-2C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00939 in 1,613,744 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0098 ( 106 hom. )

Consequence

MORN5
NM_198469.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0160

Variant links:

Genes affected

MORN5 (HGNC:17841): (MORN repeat containing 5)

MORN5 links:

NDUFA8 (HGNC:7692): (NADH:ubiquinone oxidoreductase subunit A8) The protein encoded by this gene belongs to the complex I 19 kDa subunit family. Mammalian complex I is composed of 45 different subunits. This protein has NADH dehydrogenase activity and oxidoreductase activity. It plays an important role in transfering electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

NDUFA8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 9-122159971-C-T is Benign according to our data. Variant chr9-122159971-C-T is described in ClinVar as [Benign]. Clinvar id is 1879742.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MORN5	NM_198469.4 link	c.-2C>T	5_prime_UTR_variant	Exon 1 of 5	ENST00000373764.8	NP_940871.2	Q5VZ52-1
MORN5	NM_001286828.2 link	c.-2C>T	5_prime_UTR_variant	Exon 1 of 4		NP_001273757.1	Q5VZ52A0A0A0MTF6
NDUFA8	NM_014222.3 link	c.-294G>A	upstream_gene_variant		ENST00000373768.4	NP_055037.1	P51970
NDUFA8	NM_001318195.2 link	c.-294G>A	upstream_gene_variant			NP_001305124.1	B7Z768

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MORN5	ENST00000373764 link	c.-2C>T	5_prime_UTR_variant	Exon 1 of 5	1	NM_198469.4	ENSP00000362869.3	Q5VZ52-1
MORN5	ENST00000536616 link	c.-2C>T	5_prime_UTR_variant	Exon 1 of 4	1		ENSP00000437483.2	A0A0A0MTF6
NDUFA8	ENST00000373768.4 link	c.-294G>A	upstream_gene_variant		1	NM_014222.3	ENSP00000362873.3	P51970

Frequencies

GnomAD3 genomes

AF:

0.00579

AC:

881

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00594

AC:

1491

AN:

251080

Hom.:

AF XY:

0.00583

AC XY:

792

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00242

Gnomad FIN exome

AF:

0.00370

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.00539

GnomAD4 exome

AF:

0.00976

AC:

14265

AN:

1461464

Hom.:

106

Cov.:

AF XY:

0.00941

AC XY:

6842

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00247

Gnomad4 FIN exome

AF:

0.00326

Gnomad4 NFE exome

AF:

0.0118

Gnomad4 OTH exome

AF:

0.00871

GnomAD4 genome

AF:

0.00579

AC:

881

AN:

152280

Hom.:

Cov.:

AF XY:

0.00520

AC XY:

387

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00224

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00769

Hom.:

Bravo

AF:

0.00574

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00851

EpiControl

AF:

0.00717

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MORN5: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.9

DANN

Benign

0.80

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