chr19-14566152-T-C

Variant names:

• chr19-14566152-T-C
• NM_004146.6:c.395A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004146.6(NDUFB7):​c.395A>G​(p.Asp132Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.0000055 (0 hom.)
• Consequence: NDUFB7 NM_004146.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.67
• Publications: 0 publications found

Genes affected

NDUFB7 (HGNC:7702): (NADH:ubiquinone oxidoreductase subunit B7) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is composed of 45 different subunits. It is located at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. [provided by RefSeq, Jul 2008]

TECR (HGNC:4551): (trans-2,3-enoyl-CoA reductase) This gene encodes a multi-pass membrane protein that resides in the endoplasmic reticulum, and belongs to the steroid 5-alpha reductase family. The elongation of microsomal long and very long chain fatty acid consists of 4 sequential reactions. This protein catalyzes the final step, reducing trans-2,3-enoyl-CoA to saturated acyl-CoA. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Apr 2011]

TECR Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• intellectual disability, autosomal recessive 14

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

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=0.023742408).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004146.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB7	NM_004146.6	MANE Select	c.395A>G	p.Asp132Gly	missense	Exon 3 of 3	NP_004137.2
	TECR	NM_138501.6	MANE Select	c.*281T>C		downstream_gene	N/A	NP_612510.1	Q9NZ01-1
	TECR	NM_001321170.1		c.*281T>C		downstream_gene	N/A	NP_001308099.1	Q9NZ01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB7	ENST00000215565.3	TSL:1 MANE Select	c.395A>G	p.Asp132Gly	missense	Exon 3 of 3	ENSP00000215565.1	P17568
	NDUFB7	ENST00000897442.1		c.509A>G	p.Asp170Gly	missense	Exon 4 of 4	ENSP00000567501.1
	NDUFB7	ENST00000928508.1		c.434A>G	p.Asp145Gly	missense	Exon 4 of 4	ENSP00000598567.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1459996 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726216

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 85976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111326

Other (OTH) AF: 0.0000664 AC: 4 AN: 60258

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.40
DANN	Benign	0.59
DEOGEN2	Benign	0.081	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.20	N
PhyloP100		-1.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.031
Sift	Benign	0.82	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.032
MutPred		0.10		Gain of MoRF binding (P = 0.0323)
MVP		0.12
MPC		0.19
ClinPred		0.028	T
GERP RS		-4.6
Varity_R		0.029
gMVP		0.50
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr19-14676964;