6-16141688-G-A

Variant names:

• chr6-16141688-G-A
• rs139469255
• NM_013262.4:c.342G>A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_013262.4(MYLIP):​c.342G>A​(p.Glu114Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000564 in 1,614,114 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00056 (2 hom.)
• Consequence: MYLIP NM_013262.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21

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]

MIR4639 (HGNC:41645): (microRNA 4639) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 6-16141688-G-A is Benign according to our data. Variant chr6-16141688-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1608155.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-16141688-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.21 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLIP	NM_013262.4	c.342G>A	p.Glu114Glu	synonymous_variant	Exon 3 of 7	ENST00000356840.8	NP_037394.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLIP	ENST00000356840.8	c.342G>A	p.Glu114Glu	synonymous_variant	Exon 3 of 7	1	NM_013262.4	ENSP00000349298.3
MYLIP	ENST00000349606	c.-202G>A		5_prime_UTR_variant	Exon 2 of 6	1		ENSP00000008686.6
MIR4639	ENST00000584938.1	n.*64G>A		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.000572 AC: 87 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000645 AC: 162 AN: 251312 Hom.: 1 AF XY: 0.000633 AC XY: 86 AN XY: 135824

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000578

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000995

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000563 AC: 823 AN: 1461832 Hom.: 2 Cov.: 30 AF XY: 0.000600 AC XY: 436 AN XY: 727228

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000581

Gnomad4 ASJ exome AF: 0.00149

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000613

Gnomad4 OTH exome AF: 0.000729

GnomAD4 genome AF: 0.000571 AC: 87 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.000604 AC XY: 45 AN XY: 74450

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000853

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000834 Hom.: 0

Bravo AF: 0.000631

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00131

EpiControl AF: 0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs139469255; hg19: chr6-16141919;