19-8321172-G-C

Variant names:

• chr19-8321172-G-C
• rs4147648
• NM_005001.5:c.51+136C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

ENSG00000167774 (HGNC:):

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]

RPS28 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 15 with mandibulofacial dysostosis

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005001.5. 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
	NDUFA7	NM_005001.5	MANE Select	c.51+136C>G		intron	N/A	NP_004992.2	O95182
	NDUFA7	NR_135539.2		n.68+136C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA7	ENST00000301457.3	TSL:1 MANE Select	c.51+136C>G		intron	N/A	ENSP00000301457.1	O95182
	ENSG00000167774	ENST00000598884.1	TSL:4	n.51+136C>G		intron	N/A	ENSP00000470609.1
	NDUFA7	ENST00000930188.1		c.51+136C>G		intron	N/A	ENSP00000600247.1

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

African (AFR) AF: 0.426 AC: 9758 AN: 22922

American (AMR) AF: 0.0595 AC: 1272 AN: 21376

Ashkenazi Jewish (ASJ) AF: 0.0604 AC: 1052 AN: 17414

East Asian (EAS) AF: 0.0719 AC: 2402 AN: 33396

South Asian (SAS) AF: 0.183 AC: 10795 AN: 58892

European-Finnish (FIN) AF: 0.0290 AC: 891 AN: 30760

Middle Eastern (MID) AF: 0.0755 AC: 233 AN: 3088

European-Non Finnish (NFE) AF: 0.0345 AC: 26606 AN: 771822

Other (OTH) AF: 0.0754 AC: 3340 AN: 44324

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

African (AFR) AF: 0.415 AC: 17132 AN: 41296

American (AMR) AF: 0.0767 AC: 1172 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0580 AC: 201 AN: 3466

East Asian (EAS) AF: 0.0891 AC: 459 AN: 5152

South Asian (SAS) AF: 0.208 AC: 999 AN: 4800

European-Finnish (FIN) AF: 0.0299 AC: 317 AN: 10614

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0351 AC: 2388 AN: 67966

Other (OTH) AF: 0.123 AC: 259 AN: 2112

Alfa AF: 0.102 Hom.: 249

Bravo AF: 0.164

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.4
DANN	Benign	0.53
PhyloP100		0.85
PromoterAI		0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4147648; hg19: chr19-8386056;