3-12545634-A-G

Variant names:

• chr3-12545634-A-G
• rs11706408
• NM_001378007.1:c.-89-3612T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378007.1(MKRN2OS):​c.-89-3612T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 480,938 control chromosomes in the GnomAD database, including 1,477 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 0.075 (485 hom., cov: 32)
  • Exomes 𝑓: 0.075 (992 hom.)
• Consequence: MKRN2OS NM_001378007.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 11 publications found

Genes affected

MKRN2OS (HGNC:40375): (MKRN2 opposite strand)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378007.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKRN2OS	NM_001378007.1		c.-89-3612T>C		intron	N/A	NP_001364936.1
	MKRN2OS	NM_001378008.1		c.-70-3631T>C		intron	N/A	NP_001364937.1
	MKRN2OS	NM_001195279.2	MANE Select	c.-170T>C		upstream_gene	N/A	NP_001182208.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKRN2OS	ENST00000567514.1	TSL:5	n.304-2405T>C		intron	N/A
	MKRN2OS	ENST00000678164.1		n.1068-3612T>C		intron	N/A
	MKRN2OS	ENST00000564146.4	TSL:5 MANE Select	c.-170T>C		upstream_gene	N/A	ENSP00000455385.3

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11450 AN: 152162 Hom.: 487 Cov.: 32

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0579

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.0817

GnomAD4 exome AF: 0.0751 AC: 24690 AN: 328658 Hom.: 992 AF XY: 0.0737 AC XY: 12558 AN XY: 170310

African (AFR) AF: 0.0815 AC: 722 AN: 8864

American (AMR) AF: 0.0571 AC: 562 AN: 9834

Ashkenazi Jewish (ASJ) AF: 0.0984 AC: 1093 AN: 11106

East Asian (EAS) AF: 0.000121 AC: 3 AN: 24716

South Asian (SAS) AF: 0.0308 AC: 610 AN: 19812

European-Finnish (FIN) AF: 0.0700 AC: 1781 AN: 25458

Middle Eastern (MID) AF: 0.0580 AC: 93 AN: 1604

European-Non Finnish (NFE) AF: 0.0881 AC: 18204 AN: 206688

Other (OTH) AF: 0.0788 AC: 1622 AN: 20576

GnomAD4 genome AF: 0.0752 AC: 11452 AN: 152280 Hom.: 485 Cov.: 32 AF XY: 0.0716 AC XY: 5330 AN XY: 74472

African (AFR) AF: 0.0770 AC: 3200 AN: 41554

American (AMR) AF: 0.0633 AC: 968 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5178

South Asian (SAS) AF: 0.0232 AC: 112 AN: 4826

European-Finnish (FIN) AF: 0.0579 AC: 615 AN: 10614

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0884 AC: 6011 AN: 68022

Other (OTH) AF: 0.0809 AC: 171 AN: 2114

Alfa AF: 0.0776 Hom.: 664

Bravo AF: 0.0747

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.76
PhyloP100		-0.40
PromoterAI		0.075	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11706408; hg19: chr3-12587133;