11-1996532-C-T

Position:

• chr11-1996532-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001400176.1(MRPL23):​c.498-15009C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: MRPL23 NM_001400176.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.863

Genes affected

H19 (HGNC:4713): (H19 imprinted maternally expressed transcript) This gene is located in an imprinted region of chromosome 11 near the insulin-like growth factor 2 (IGF2) gene. This gene is only expressed from the maternally-inherited chromosome, whereas IGF2 is only expressed from the paternally-inherited chromosome. The product of this gene is a long non-coding RNA which functions as a tumor suppressor. Mutations in this gene have been associated with Beckwith-Wiedemann Syndrome and Wilms tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

MRPL23 (HGNC:10322): (mitochondrial ribosomal protein L23) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. The gene is biallelically expressed, despite its location within a region of imprinted genes on chromosome 11. [provided by RefSeq, Jul 2008]

ENSG00000275266 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 11-1996532-C-T is Benign according to our data. Variant chr11-1996532-C-T is described in ClinVar as [Benign]. Clinvar id is 3024686.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL23	NM_001400176.1	c.498-15009C>T		intron_variant			NP_001387105.1
MRPL23	XM_011520273.2	c.498-15009C>T		intron_variant			XP_011518575.1
H19	NR_002196.3	n.1311G>A		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H19	ENST00000412788.6	n.1311G>A		non_coding_transcript_exon_variant	1/5	1
H19	ENST00000414790.9	n.1312G>A		non_coding_transcript_exon_variant	1/5	1
H19	ENST00000411861.6	n.1311G>A		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.00681 AC: 895 AN: 131374 Hom.: 8 AF XY: 0.00776 AC XY: 556 AN XY: 71612

Gnomad AFR exome AF: 0.00194

Gnomad AMR exome AF: 0.00144

Gnomad ASJ exome AF: 0.000890

Gnomad EAS exome AF: 0.0000950

Gnomad SAS exome AF: 0.00962

Gnomad FIN exome AF: 0.00115

Gnomad NFE exome AF: 0.0121

Gnomad OTH exome AF: 0.00542

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.00405 Hom.: 0

Asia WGS AF: 0.00231 AC: 8 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

H19: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.6
DANN	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs377448027; hg19: chr11-2017762;