NM_013255.5:c.98+8343G>A

Variant names:

• chr7-131336340-G-A
• rs7807274
• NM_013255.5:c.98+8343G>A

Variant summary

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

The NM_013255.5(MKLN1):​c.98+8343G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 151,820 control chromosomes in the GnomAD database, including 432 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 0.044 (432 hom., cov: 32)
• Consequence: MKLN1 NM_013255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013255.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKLN1	NM_013255.5	MANE Select	c.98+8343G>A		intron	N/A	NP_037387.2
	MKLN1	NM_001145354.2		c.30-39084G>A		intron	N/A	NP_001138826.1	B4DG30
	MKLN1	NM_001321316.2		c.-527+8343G>A		intron	N/A	NP_001308245.1	Q9UL63-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKLN1	ENST00000352689.11	TSL:1 MANE Select	c.98+8343G>A		intron	N/A	ENSP00000323527.6	Q9UL63-1
	MKLN1	ENST00000494785.5	TSL:1	n.115+8343G>A		intron	N/A
	MKLN1	ENST00000861935.1		c.98+8343G>A		intron	N/A	ENSP00000531994.1

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6708 AN: 151702 Hom.: 431 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00155

Gnomad OTH AF: 0.0356

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

GnomAD4 genome AF: 0.0443 AC: 6721 AN: 151820 Hom.: 432 Cov.: 32 AF XY: 0.0421 AC XY: 3122 AN XY: 74214

African (AFR) AF: 0.149 AC: 6192 AN: 41426

American (AMR) AF: 0.0218 AC: 332 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00155 AC: 105 AN: 67840

Other (OTH) AF: 0.0352 AC: 74 AN: 2100

Alfa AF: 0.0670 Hom.: 218

Bravo AF: 0.0506

Asia WGS AF: 0.00868 AC: 30 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.65
PhyloP100		-0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7807274; hg19: chr7-131021099;