7-131327925-C-G

Variant names:

• chr7-131327925-C-G
• rs200265321
• NM_013255.5:c.26C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013255.5(MKLN1):​c.26C>G​(p.Ala9Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A9V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MKLN1 NM_013255.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• Publications: 4 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]

MKLN1-AS (HGNC:40374): (MKLN1 antisense RNA)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.118355125).

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.26C>G	p.Ala9Gly	missense	Exon 1 of 18	NP_037387.2
	MKLN1	NM_001321316.2		c.-599C>G		5_prime_UTR	Exon 1 of 18	NP_001308245.1	Q9UL63-2
	MKLN1	NM_001145354.2		c.30-47499C>G		intron	N/A	NP_001138826.1	B4DG30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKLN1	ENST00000352689.11	TSL:1 MANE Select	c.26C>G	p.Ala9Gly	missense	Exon 1 of 18	ENSP00000323527.6	Q9UL63-1
	MKLN1	ENST00000494785.5	TSL:1	n.43C>G		non_coding_transcript_exon	Exon 1 of 17
	MKLN1	ENST00000861935.1		c.26C>G	p.Ala9Gly	missense	Exon 1 of 19	ENSP00000531994.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460804 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726774

African (AFR) AF: 0.0000299 AC: 1 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111796

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.50
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.027
Sift	Benign	0.21	T
Sift4G	Benign	0.63	T
Polyphen		0.013	B
Vest4		0.40
MutPred		0.33		Gain of relative solvent accessibility (P = 0.0023)
MVP		0.23
MPC		0.48
ClinPred		0.26	T
GERP RS		1.3
PromoterAI		-0.15	Neutral
Varity_R		0.049
gMVP		0.38
Mutation Taster		=80/20	polymorphism

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: rs200265321; hg19: chr7-131012684; COSMIC: COSV100759878; COSMIC: COSV100759878;