chr12-69958513-C-T

Variant names:

• chr12-69958513-C-T
• rs200704226
• NM_182530.3:c.2715C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_182530.3(MYRFL):​c.2715C>T​(p.Phe905Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000678 in 1,534,772 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (10 hom.)
• Consequence: MYRFL NM_182530.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.777
• Publications: 0 publications found

Genes affected

MYRFL (HGNC:26316): (myelin regulatory factor like) Predicted to enable DNA-binding transcription factor activity and sequence-specific DNA binding activity. Predicted to be involved in positive regulation of transcription, DNA-templated and protein autoprocessing. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PRANCR (HGNC:51126): (progenitor renewal associated non-coding RNA)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.077).
• BP6: Variant 12-69958513-C-T is Benign according to our data. Variant chr12-69958513-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2643174.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.777 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182530.3. 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
	MYRFL	NM_182530.3	MANE Select	c.2715C>T	p.Phe905Phe	synonymous	Exon 25 of 25	NP_872336.2	Q96LU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRFL	ENST00000552032.7	TSL:5 MANE Select	c.2715C>T	p.Phe905Phe	synonymous	Exon 25 of 25	ENSP00000448753.2	Q96LU7
	MYRFL	ENST00000535034.6	TSL:1	c.2640C>T	p.Phe880Phe	synonymous	Exon 24 of 24	ENSP00000440626.2
	MYRFL	ENST00000547771.6	TSL:5	c.2679C>T	p.Phe893Phe	synonymous	Exon 25 of 25	ENSP00000449598.2	F8VVR8

Frequencies

GnomAD3 genomes AF: 0.000738 AC: 112 AN: 151766 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000574

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00131 AC: 178 AN: 136350 AF XY: 0.00120

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000328

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000430

Gnomad OTH exome AF: 0.000954

GnomAD4 exome AF: 0.000672 AC: 929 AN: 1382890 Hom.: 10 Cov.: 31 AF XY: 0.000651 AC XY: 444 AN XY: 682344

African (AFR) AF: 0.0000951 AC: 3 AN: 31552

American (AMR) AF: 0.000281 AC: 10 AN: 35642

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 486 AN: 25164

East Asian (EAS) AF: 0.00 AC: 0 AN: 35698

South Asian (SAS) AF: 0.00 AC: 0 AN: 78958

European-Finnish (FIN) AF: 0.0000295 AC: 1 AN: 33878

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5608

European-Non Finnish (NFE) AF: 0.000323 AC: 348 AN: 1078524

Other (OTH) AF: 0.00138 AC: 80 AN: 57866

GnomAD4 genome AF: 0.000737 AC: 112 AN: 151882 Hom.: 0 Cov.: 32 AF XY: 0.000701 AC XY: 52 AN XY: 74210

African (AFR) AF: 0.0000483 AC: 2 AN: 41392

American (AMR) AF: 0.000131 AC: 2 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000574 AC: 39 AN: 67968

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.00290 Hom.: 1

Bravo AF: 0.000740

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	7.8
DANN	Benign	0.80
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs200704226; hg19: chr12-70352293;