NM_001145354.2:c.-93-14482C>A

Variant names:

• chr7-131128338-C-A
• rs6974649
• NM_001145354.2:c.-93-14482C>A

Variant summary

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

The NM_001145354.2(MKLN1):​c.-93-14482C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,790 control chromosomes in the GnomAD database, including 15,622 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 0.43 (15622 hom., cov: 31)
• Consequence: MKLN1 NM_001145354.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• Publications: 8 publications found

Genes affected

MKLN1 (HGNC:7109): (muskelin 1) Muskelin is an intracellular protein that acts as a mediator of cell spreading and cytoskeletal responses to the extracellular matrix component thrombospondin I (MIM 188060) (Adams et al., 1998 [PubMed 9724633]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKLN1	NM_001145354.2	c.-93-14482C>A		intron_variant	Intron 1 of 18		NP_001138826.1
MKLN1	XM_047420401.1	c.-93-14482C>A		intron_variant	Intron 1 of 18		XP_047276357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MKLN1	ENST00000421797.6	c.-300-14482C>A		intron_variant	Intron 1 of 18	2		ENSP00000398094.2
MKLN1	ENST00000416992.6	c.-418-14482C>A		intron_variant	Intron 1 of 7	3		ENSP00000387920.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64707 AN: 151680 Hom.: 15620 Cov.: 31

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.410

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.426 AC: 64730 AN: 151790 Hom.: 15622 Cov.: 31 AF XY: 0.419 AC XY: 31099 AN XY: 74178

African (AFR) AF: 0.258 AC: 10671 AN: 41382

American (AMR) AF: 0.347 AC: 5298 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1673 AN: 3466

East Asian (EAS) AF: 0.152 AC: 785 AN: 5162

South Asian (SAS) AF: 0.193 AC: 928 AN: 4812

European-Finnish (FIN) AF: 0.553 AC: 5801 AN: 10488

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38112 AN: 67916

Other (OTH) AF: 0.406 AC: 856 AN: 2108

Alfa AF: 0.506 Hom.: 66864

Bravo AF: 0.406

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.3
DANN	Benign	0.72
PhyloP100		0.49
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: rs6974649; hg19: chr7-130813097;