rs10488386

Variant names:

• chr7-131216067-T-A
• rs10488386
• NM_001145354.2:c.29+73126T>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.29+73126T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,090 control chromosomes in the GnomAD database, including 2,858 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 0.18 (2858 hom., cov: 31)
• Consequence: MKLN1 NM_001145354.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKLN1	NM_001145354.2	c.29+73126T>A		intron_variant	Intron 2 of 18		NP_001138826.1
MKLN1	XM_047420401.1	c.29+73126T>A		intron_variant	Intron 2 of 18		XP_047276357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MKLN1	ENST00000421797.6	c.-179+73126T>A		intron_variant	Intron 2 of 18	2		ENSP00000398094.2
MKLN1	ENST00000416992.6	c.-179+13093T>A		intron_variant	Intron 3 of 7	3		ENSP00000387920.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26808 AN: 151972 Hom.: 2859 Cov.: 31

Gnomad AFR AF: 0.0852

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.0754

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.176 AC: 26815 AN: 152090 Hom.: 2858 Cov.: 31 AF XY: 0.172 AC XY: 12822 AN XY: 74350

African (AFR) AF: 0.0850 AC: 3526 AN: 41500

American (AMR) AF: 0.142 AC: 2163 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3468

East Asian (EAS) AF: 0.0241 AC: 125 AN: 5182

South Asian (SAS) AF: 0.0765 AC: 369 AN: 4826

European-Finnish (FIN) AF: 0.226 AC: 2391 AN: 10570

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16742 AN: 67956

Other (OTH) AF: 0.182 AC: 383 AN: 2110

Alfa AF: 0.215 Hom.: 484

Bravo AF: 0.167

Asia WGS AF: 0.0700 AC: 245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.81
PhyloP100		-0.27
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: rs10488386; hg19: chr7-130900826;