rs6960667

Variant names:

• chr7-131238686-A-G
• rs6960667
• NM_001145354.2:c.29+95745A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001145354.2(MKLN1):​c.29+95745A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 152,350 control chromosomes in the GnomAD database, including 112 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 0.033 (112 hom., cov: 32)
• Consequence: MKLN1 NM_001145354.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• Publications: 3 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).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0333 (5080/152350) while in subpopulation NFE AF = 0.0505 (3435/68030). AF 95% confidence interval is 0.0491. There are 112 homozygotes in GnomAd4. There are 2341 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5080 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145354.2. 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
	MKLN1	NM_001145354.2		c.29+95745A>G		intron	N/A	NP_001138826.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKLN1	ENST00000421797.6	TSL:2	c.-179+95745A>G		intron	N/A	ENSP00000398094.2
	MKLN1	ENST00000416992.6	TSL:3	c.-179+35712A>G		intron	N/A	ENSP00000387920.1

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5082 AN: 152232 Hom.: 112 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00434

Gnomad FIN AF: 0.0329

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0505

Gnomad OTH AF: 0.0406

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

GnomAD4 genome AF: 0.0333 AC: 5080 AN: 152350 Hom.: 112 Cov.: 32 AF XY: 0.0314 AC XY: 2341 AN XY: 74500

African (AFR) AF: 0.0102 AC: 426 AN: 41590

American (AMR) AF: 0.0424 AC: 649 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00455 AC: 22 AN: 4832

European-Finnish (FIN) AF: 0.0329 AC: 349 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0505 AC: 3435 AN: 68030

Other (OTH) AF: 0.0402 AC: 85 AN: 2116

Alfa AF: 0.0447 Hom.: 103

Bravo AF: 0.0344

Asia WGS AF: 0.00318 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.62
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs6960667; hg19: chr7-130923445;