rs4746821

Positions:

• chr10-69208443-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003171.5(SUPV3L1):​c.1926-157G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,206 control chromosomes in the GnomAD database, including 4,610 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4610 hom., cov: 32)
• Consequence: SUPV3L1 NM_003171.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

Genes affected

SUPV3L1 (HGNC:11471): (Suv3 like RNA helicase) Enables helicase activity; nucleic acid binding activity; and protein homodimerization activity. Involved in several processes, including mitochondrial RNA metabolic process; mitochondrion morphogenesis; and positive regulation of mitochondrial RNA catabolic process. Located in mitochondrial nucleoid and nucleus. Part of mitochondrial degradosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUPV3L1	NM_003171.5	c.1926-157G>T		intron_variant		ENST00000359655.9	NP_003162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUPV3L1	ENST00000359655.9	c.1926-157G>T		intron_variant		1	NM_003171.5	ENSP00000352678.4
SUPV3L1	ENST00000497254.1	n.167-157G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33475 AN: 152088 Hom.: 4608 Cov.: 32

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.220 AC: 33478 AN: 152206 Hom.: 4610 Cov.: 32 AF XY: 0.220 AC XY: 16345 AN XY: 74398

Gnomad4 AFR AF: 0.0570

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.218

Alfa AF: 0.291 Hom.: 3904

Bravo AF: 0.207

Asia WGS AF: 0.167 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.21
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs4746821; hg19: chr10-70968199;