7-131216067-T-A

Position:

• chr7-131216067-T-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MKLN1	NM_001145354.2	c.29+73126T>A		intron_variant			NP_001138826.1
MKLN1	XM_047420401.1	c.29+73126T>A		intron_variant			XP_047276357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKLN1	ENST00000416992.6	c.-179+13093T>A		intron_variant		3		ENSP00000387920
MKLN1	ENST00000421797.6	c.-179+73126T>A		intron_variant		2		ENSP00000398094

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

Gnomad4 AFR AF: 0.0850

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.0241

Gnomad4 SAS AF: 0.0765

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.182

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10488386; hg19: chr7-130900826;