chr19-8321172-G-C

Position:

• chr19-8321172-G-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_005001.5(NDUFA7):​c.51+136C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 1,155,882 control chromosomes in the GnomAD database, including 7,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (3811 hom., cov: 32)
  • Exomes 𝑓: 0.056 (4179 hom.)
• Consequence: NDUFA7 NM_005001.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.855

Genes affected

NDUFA7 (HGNC:7691): (NADH:ubiquinone oxidoreductase subunit A7) This gene encodes a subunit of NADH:ubiquinone oxidoreductase (complex I), which is a multiprotein complex located in the inner mitochondrial membrane. Complex I functions in the transfer of electrons from NADH to the respiratory chain. [provided by RefSeq, Mar 2011]

RPS28 (HGNC:10418): (ribosomal protein S28) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S28E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 19-8321172-G-C is Benign according to our data. Variant chr19-8321172-G-C is described in ClinVar as [Benign]. Clinvar id is 1224045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA7	NM_005001.5	c.51+136C>G		intron_variant		ENST00000301457.3	NP_004992.2
NDUFA7	NR_135539.2	n.68+136C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA7	ENST00000301457.3	c.51+136C>G		intron_variant		1	NM_005001.5	ENSP00000301457	P1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22910 AN: 151770 Hom.: 3793 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0768

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.0889

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.0561 AC: 56349 AN: 1003994 Hom.: 4179 Cov.: 14 AF XY: 0.0593 AC XY: 29409 AN XY: 496016

Gnomad4 AFR exome AF: 0.426

Gnomad4 AMR exome AF: 0.0595

Gnomad4 ASJ exome AF: 0.0604

Gnomad4 EAS exome AF: 0.0719

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.0290

Gnomad4 NFE exome AF: 0.0345

Gnomad4 OTH exome AF: 0.0754

GnomAD4 genome AF: 0.151 AC: 22970 AN: 151888 Hom.: 3811 Cov.: 32 AF XY: 0.152 AC XY: 11276 AN XY: 74260

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.0767

Gnomad4 ASJ AF: 0.0580

Gnomad4 EAS AF: 0.0891

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.0299

Gnomad4 NFE AF: 0.0351

Gnomad4 OTH AF: 0.123

Alfa AF: 0.102 Hom.: 249

Bravo AF: 0.164

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.4
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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

LitVar

Other links and lift over

dbSNP: rs4147648; hg19: chr19-8386056;