chr6-54137659-T-G

Variant names:

• chr6-54137659-T-G
• rs368911145
• NM_001281747.2:c.1590T>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001281747.2(MLIP):​c.1590T>G​(p.Thr530Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,536,070 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (88 hom.)
• Consequence: MLIP NM_001281747.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.488
• Publications: 0 publications found

Genes affected

MLIP (HGNC:21355): (muscular LMNA interacting protein) Predicted to enable lamin binding activity and transcription corepressor activity. Predicted to be involved in negative regulation of cardiac muscle hypertrophy in response to stress; negative regulation of transcription by RNA polymerase II; and positive regulation of transcription by RNA polymerase II. Predicted to be located in nuclear lumen. Predicted to be active in PML body; nuclear envelope; and sarcolemma. [provided by Alliance of Genome Resources, Apr 2022]

MLIP Gene-Disease associations (from GenCC):

• myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-54137659-T-G is Benign according to our data. Variant chr6-54137659-T-G is described in ClinVar as Benign. ClinVar VariationId is 3668095.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.488 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00142 (216/152270) while in subpopulation SAS AF = 0.0408 (197/4828). AF 95% confidence interval is 0.0361. There are 4 homozygotes in GnomAd4. There are 154 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281747.2. 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
	MLIP	NM_001281747.2	MANE Select	c.1590T>G	p.Thr530Thr	synonymous	Exon 4 of 14	NP_001268676.1	Q5VWP3-3
	MLIP	NM_001281746.2		c.1557T>G	p.Thr519Thr	synonymous	Exon 4 of 12	NP_001268675.1	Q5VWP3-4
	MLIP	NM_138569.3		c.613-11397T>G		intron	N/A	NP_612636.2	Q5VWP3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLIP	ENST00000502396.6	TSL:2 MANE Select	c.1590T>G	p.Thr530Thr	synonymous	Exon 4 of 14	ENSP00000426290.1	Q5VWP3-3
	MLIP	ENST00000514921.5	TSL:1	c.1557T>G	p.Thr519Thr	synonymous	Exon 4 of 12	ENSP00000425142.1	Q5VWP3-4
	MLIP	ENST00000370876.6	TSL:1	c.426+12794T>G		intron	N/A	ENSP00000359913.2	Q5VWP3-2

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 215 AN: 152152 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0406

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00643 AC: 862 AN: 133972 AF XY: 0.00858

Gnomad AFR exome AF: 0.000155

Gnomad AMR exome AF: 0.000368

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000952

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.00242

GnomAD4 exome AF: 0.00228 AC: 3153 AN: 1383800 Hom.: 88 Cov.: 34 AF XY: 0.00331 AC XY: 2263 AN XY: 682846

African (AFR) AF: 0.000253 AC: 8 AN: 31592

American (AMR) AF: 0.000336 AC: 12 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35734

South Asian (SAS) AF: 0.0361 AC: 2861 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33890

Middle Eastern (MID) AF: 0.00193 AC: 11 AN: 5696

European-Non Finnish (NFE) AF: 0.0000992 AC: 107 AN: 1078870

Other (OTH) AF: 0.00263 AC: 152 AN: 57902

GnomAD4 genome AF: 0.00142 AC: 216 AN: 152270 Hom.: 4 Cov.: 32 AF XY: 0.00207 AC XY: 154 AN XY: 74464

African (AFR) AF: 0.0000481 AC: 2 AN: 41562

American (AMR) AF: 0.000654 AC: 10 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000128 Hom.: 0

Bravo AF: 0.000295

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.36
PhyloP100		0.49
Mutation Taster		=100/0	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: rs368911145; hg19: chr6-54002457;