rs6960667

Positions:

• chr7-131238686-A-G

Variant summary

Our verdict is Benign. Variant got -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

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).
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5080 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKLN1	NM_001145354.2	c.29+95745A>G		intron_variant			NP_001138826.1
MKLN1	XM_047420401.1	c.29+95745A>G		intron_variant			XP_047276357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKLN1	ENST00000416992.6	c.-179+35712A>G		intron_variant		3		ENSP00000387920
MKLN1	ENST00000421797.6	c.-179+95745A>G		intron_variant		2		ENSP00000398094

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

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00455

Gnomad4 FIN AF: 0.0329

Gnomad4 NFE AF: 0.0505

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0418 Hom.: 53

Bravo AF: 0.0344

Asia WGS AF: 0.00318 AC: 12 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	3.8
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6960667; hg19: chr7-130923445;