chr16-715584-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -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 VariationId is 3395238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.386 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024042.4. 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
	METRN	NM_024042.4	MANE Select	c.105C>T	p.Ser35Ser	splice_region synonymous	Exon 2 of 4	NP_076947.1	Q9UJH8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METRN	ENST00000568223.7	TSL:1 MANE Select	c.105C>T	p.Ser35Ser	splice_region synonymous	Exon 2 of 4	ENSP00000455068.1	Q9UJH8
	METRN	ENST00000936477.1		c.129C>T	p.Ser43Ser	synonymous	Exon 2 of 4	ENSP00000606536.1
	METRN	ENST00000219542.3	TSL:2	c.57C>T	p.Ser19Ser	splice_region synonymous	Exon 2 of 3	ENSP00000219542.3	J3KMW6

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

African (AFR) AF: 0.00 AC: 0 AN: 23874

American (AMR) AF: 0.00 AC: 0 AN: 11806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17040

East Asian (EAS) AF: 0.00 AC: 0 AN: 27140

South Asian (SAS) AF: 0.00 AC: 0 AN: 50738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3370

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 990972

Other (OTH) AF: 0.00 AC: 0 AN: 48670

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		-0.39
PromoterAI		-0.022	Neutral

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

Other links and lift over

hg19: chr16-765584;