chr11-48978871-C-G

Variant names:

• chr11-48978871-C-G
• rs1965370
• NM_001396075.1:c.738+1G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PVS1_Strong BA1

The NM_001396075.1(TRIM51G):​c.738+1G>C variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 1,307,198 control chromosomes in the GnomAD database, including 407,607 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 0.80 (48531 hom., cov: 32)
  • Exomes 𝑓: 0.79 (359076 hom.)
• Consequence: TRIM51G NM_001396075.1 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.823

Genes affected

TRIM51G (HGNC:43972): (tripartite motif-containing 51G) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.16997792 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM51G	NM_001396075.1	c.738+1G>C		splice_donor_variant, intron_variant	Intron 4 of 6	ENST00000534741.3	NP_001383004.1
TRIM51G	XM_047426375.1	c.508-711G>C		intron_variant	Intron 2 of 4		XP_047282331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM51G	ENST00000534741.3	c.738+1G>C		splice_donor_variant, intron_variant	Intron 4 of 6	6	NM_001396075.1	ENSP00000497050.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121065 AN: 151938 Hom.: 48490 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.777

GnomAD3 exomes AF: 0.766 AC: 189591 AN: 247586 Hom.: 73700 AF XY: 0.755 AC XY: 101366 AN XY: 134334

Gnomad AFR exome AF: 0.810

Gnomad AMR exome AF: 0.806

Gnomad ASJ exome AF: 0.768

Gnomad EAS exome AF: 0.621

Gnomad SAS exome AF: 0.570

Gnomad FIN exome AF: 0.836

Gnomad NFE exome AF: 0.810

Gnomad OTH exome AF: 0.775

GnomAD4 exome AF: 0.785 AC: 906945 AN: 1155142 Hom.: 359076 Cov.: 16 AF XY: 0.778 AC XY: 459090 AN XY: 589936

Gnomad4 AFR exome AF: 0.798

Gnomad4 AMR exome AF: 0.803

Gnomad4 ASJ exome AF: 0.759

Gnomad4 EAS exome AF: 0.663

Gnomad4 SAS exome AF: 0.575

Gnomad4 FIN exome AF: 0.836

Gnomad4 NFE exome AF: 0.809

Gnomad4 OTH exome AF: 0.766

GnomAD4 genome AF: 0.797 AC: 121165 AN: 152056 Hom.: 48531 Cov.: 32 AF XY: 0.793 AC XY: 58901 AN XY: 74300

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.777

Alfa AF: 0.802 Hom.: 8983

Bravo AF: 0.797

TwinsUK AF: 0.824 AC: 3055

ALSPAC AF: 0.818 AC: 3153

ExAC AF: 0.762 AC: 92297

Asia WGS AF: 0.589 AC: 2049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	14
DANN	Benign	0.21
FATHMM_MKL	Benign	0.015	N
GERP RS		0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1965370; hg19: chr11-49000423;