NM_013262.4:c.1173C>T

Variant names:

• chr6-16145242-C-T
• rs1060901
• NM_013262.4:c.1173C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_013262.4(MYLIP):​c.1173C>T​(p.Cys391Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 1,613,460 control chromosomes in the GnomAD database, including 6,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (374 hom., cov: 32)
  • Exomes 𝑓: 0.084 (5705 hom.)
• Consequence: MYLIP NM_013262.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.201
• Publications: 13 publications found

Genes affected

MYLIP (HGNC:21155): (myosin regulatory light chain interacting protein) The ERM protein family members ezrin, radixin, and moesin are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. Myosin regulatory light chain interacting protein (MYLIP) is a novel ERM-like protein that interacts with myosin regulatory light chain and inhibits neurite outgrowth. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 6-16145242-C-T is Benign according to our data. Variant chr6-16145242-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1601611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.201 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0931 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013262.4. 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
	MYLIP	NM_013262.4	MANE Select	c.1173C>T	p.Cys391Cys	synonymous	Exon 6 of 7	NP_037394.2
	MYLIP	NM_001436627.1		c.1008C>T	p.Cys336Cys	synonymous	Exon 5 of 6	NP_001423556.1	A0ABB0MVD9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLIP	ENST00000356840.8	TSL:1 MANE Select	c.1173C>T	p.Cys391Cys	synonymous	Exon 6 of 7	ENSP00000349298.3	Q8WY64-1
	MYLIP	ENST00000349606.5	TSL:1	n.*757C>T		non_coding_transcript_exon	Exon 5 of 6	ENSP00000008686.6	Q5TIA5
	MYLIP	ENST00000349606.5	TSL:1	n.*757C>T		3_prime_UTR	Exon 5 of 6	ENSP00000008686.6	Q5TIA5

Frequencies

GnomAD3 genomes AF: 0.0622 AC: 9459 AN: 152120 Hom.: 374 Cov.: 32

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0420

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.0564

GnomAD2 exomes AF: 0.0658 AC: 16497 AN: 250772 AF XY: 0.0660

Gnomad AFR exome AF: 0.0131

Gnomad AMR exome AF: 0.0332

Gnomad ASJ exome AF: 0.0572

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.0950

Gnomad OTH exome AF: 0.0712

GnomAD4 exome AF: 0.0841 AC: 122866 AN: 1461222 Hom.: 5705 Cov.: 34 AF XY: 0.0826 AC XY: 60005 AN XY: 726798

African (AFR) AF: 0.0132 AC: 443 AN: 33472

American (AMR) AF: 0.0345 AC: 1542 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0563 AC: 1471 AN: 26122

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39678

South Asian (SAS) AF: 0.0255 AC: 2199 AN: 86238

European-Finnish (FIN) AF: 0.121 AC: 6451 AN: 53356

Middle Eastern (MID) AF: 0.0379 AC: 218 AN: 5754

European-Non Finnish (NFE) AF: 0.0955 AC: 106107 AN: 1111550

Other (OTH) AF: 0.0732 AC: 4420 AN: 60354

GnomAD4 genome AF: 0.0621 AC: 9454 AN: 152238 Hom.: 374 Cov.: 32 AF XY: 0.0610 AC XY: 4539 AN XY: 74432

African (AFR) AF: 0.0156 AC: 649 AN: 41564

American (AMR) AF: 0.0420 AC: 642 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 189 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5172

South Asian (SAS) AF: 0.0234 AC: 113 AN: 4822

European-Finnish (FIN) AF: 0.112 AC: 1188 AN: 10590

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0950 AC: 6463 AN: 67998

Other (OTH) AF: 0.0549 AC: 116 AN: 2114

Alfa AF: 0.0817 Hom.: 291

Bravo AF: 0.0553

Asia WGS AF: 0.0140 AC: 48 AN: 3478

EpiCase AF: 0.0884

EpiControl AF: 0.0849

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	3.8
DANN	Benign	0.82
PhyloP100		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs1060901; hg19: chr6-16145473; COSMIC: COSV62766793; COSMIC: COSV62766793;