19-5893056-T-C

Position:

• chr19-5893056-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001193375.3(NDUFA11):​c.548A>G​(p.Glu183Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NDUFA11 NM_001193375.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.103

Genes affected

ENSG00000267740 (HGNC:):

NDUFA11 (HGNC:20371): (NADH:ubiquinone oxidoreductase subunit A11) This gene encodes a subunit of the membrane-bound mitochondrial complex I. Complex I is composed of numerous subunits and functions as the NADH-ubiquinol reductase of the mitochondrial electron transport chain. Mutations in this gene are associated with severe mitochondrial complex I deficiency. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045683295).
• BP6: Variant 19-5893056-T-C is Benign according to our data. Variant chr19-5893056-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2261182.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA11	NM_001193375.3	c.548A>G	p.Glu183Gly	missense_variant	4/4		NP_001180304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000267740	ENST00000586349.5	c.382+3397A>G		intron_variant		2		ENSP00000466639.1
NDUFA11	ENST00000418389.6	c.548A>G	p.Glu183Gly	missense_variant	4/4	2		ENSP00000389160.1
ENSG00000267740	ENST00000585661.1	c.307+3397A>G		intron_variant		2		ENSP00000467210.1
ENSG00000267740	ENST00000592091.5	n.313+3397A>G		intron_variant		2		ENSP00000465499.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.4
DANN	Benign	0.93
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0066	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.077
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.46	T
Vest4		0.092
MutPred		0.12		Gain of loop (P = 0.0166);
MVP		0.043
MPC		0.24
ClinPred		0.057	T
GERP RS		-2.1
gMVP		0.063

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-5893067;