chr6-16145094-A-G

Variant names:

• chr6-16145094-A-G
• rs9370867
• NM_013262.4:c.1025A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013262.4(MYLIP):​c.1025A>G​(p.Asn342Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,613,978 control chromosomes in the GnomAD database, including 237,883 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (33294 hom., cov: 33)
  • Exomes 𝑓: 0.51 (204589 hom.)
• Consequence: MYLIP NM_013262.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.97
• Publications: 64 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.170516E-7).
• BP6: Variant 6-16145094-A-G is Benign according to our data. Variant chr6-16145094-A-G is described in ClinVar as Benign. ClinVar VariationId is 1598643.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLIP	NM_013262.4	MANE Select	c.1025A>G	p.Asn342Ser	missense	Exon 6 of 7	NP_037394.2
	MYLIP	NM_001436627.1		c.860A>G	p.Asn287Ser	missense	Exon 5 of 6	NP_001423556.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLIP	ENST00000356840.8	TSL:1 MANE Select	c.1025A>G	p.Asn342Ser	missense	Exon 6 of 7	ENSP00000349298.3
	MYLIP	ENST00000349606.5	TSL:1	n.*609A>G		non_coding_transcript_exon	Exon 5 of 6	ENSP00000008686.6
	MYLIP	ENST00000349606.5	TSL:1	n.*609A>G		3_prime_UTR	Exon 5 of 6	ENSP00000008686.6

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96171 AN: 152006 Hom.: 33227 Cov.: 33

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.589

GnomAD2 exomes AF: 0.600 AC: 150922 AN: 251402 AF XY: 0.587

Gnomad AFR exome AF: 0.905

Gnomad AMR exome AF: 0.740

Gnomad ASJ exome AF: 0.515

Gnomad EAS exome AF: 0.949

Gnomad FIN exome AF: 0.469

Gnomad NFE exome AF: 0.483

Gnomad OTH exome AF: 0.560

GnomAD4 exome AF: 0.515 AC: 752166 AN: 1461854 Hom.: 204589 Cov.: 72 AF XY: 0.516 AC XY: 375521 AN XY: 727224

African (AFR) AF: 0.912 AC: 30528 AN: 33480

American (AMR) AF: 0.732 AC: 32740 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 13282 AN: 26136

East Asian (EAS) AF: 0.966 AC: 38370 AN: 39700

South Asian (SAS) AF: 0.636 AC: 54836 AN: 86254

European-Finnish (FIN) AF: 0.482 AC: 25765 AN: 53414

Middle Eastern (MID) AF: 0.503 AC: 2903 AN: 5768

European-Non Finnish (NFE) AF: 0.468 AC: 520833 AN: 1111986

Other (OTH) AF: 0.545 AC: 32909 AN: 60392

GnomAD4 genome AF: 0.633 AC: 96301 AN: 152124 Hom.: 33294 Cov.: 33 AF XY: 0.633 AC XY: 47055 AN XY: 74364

African (AFR) AF: 0.897 AC: 37277 AN: 41542

American (AMR) AF: 0.645 AC: 9860 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1792 AN: 3468

East Asian (EAS) AF: 0.948 AC: 4900 AN: 5170

South Asian (SAS) AF: 0.652 AC: 3140 AN: 4814

European-Finnish (FIN) AF: 0.458 AC: 4843 AN: 10564

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32685 AN: 67956

Other (OTH) AF: 0.593 AC: 1252 AN: 2110

Alfa AF: 0.537 Hom.: 107467

Bravo AF: 0.660

TwinsUK AF: 0.462 AC: 1713

ALSPAC AF: 0.466 AC: 1797

ESP6500AA AF: 0.887 AC: 3906

ESP6500EA AF: 0.476 AC: 4094

ExAC AF: 0.606 AC: 73628

Asia WGS AF: 0.835 AC: 2904 AN: 3478

EpiCase AF: 0.468

EpiControl AF: 0.468

ClinVar

ClinVar submissions as Germline

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
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.9
DANN	Benign	0.64
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	6.2e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.035	N
PhyloP100		2.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.016
MPC		0.14
ClinPred		0.0018	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.13
Mutation Taster		=98/2	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: rs9370867; hg19: chr6-16145325; COSMIC: COSV62766341; COSMIC: COSV62766341;