16-715584-C-T

Variant names:

• chr16-715584-C-T
• NM_024042.4:c.105C>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_024042.4(METRN):​c.105C>T​(p.Ser35Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: METRN NM_024042.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0005407
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.386

Genes affected

METRN (HGNC:14151): (meteorin, glial cell differentiation regulator) Meteorin regulates glial cell differentiation and promotes the formation of axonal networks during neurogenesis (Nishino et al., 2004 [PubMed 15085178]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 16-715584-C-T is Benign according to our data. Variant chr16-715584-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3395238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.386 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METRN	NM_024042.4	c.105C>T	p.Ser35Ser	splice_region_variant, synonymous_variant	Exon 2 of 4	ENST00000568223.7	NP_076947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METRN	ENST00000568223.7	c.105C>T	p.Ser35Ser	splice_region_variant, synonymous_variant	Exon 2 of 4	1	NM_024042.4	ENSP00000455068.1
METRN	ENST00000219542.3	c.57C>T	p.Ser19Ser	splice_region_variant, synonymous_variant	Exon 2 of 3	2		ENSP00000219542.3
METRN	ENST00000570132.1	n.104+191C>T		intron_variant	Intron 1 of 3	3		ENSP00000456647.1
METRN	ENST00000567076.5	c.-58C>T		upstream_gene_variant		5		ENSP00000459900.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1202248 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 586322

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 26, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00054
dbscSNV1_RF	Benign	0.11
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-765584;