NM_006343.3:c.62-8727G>T

Variant names:

• chr2-111920393-G-T
• rs867311
• NM_006343.3:c.62-8727G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006343.3(MERTK):​c.62-8727G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,984 control chromosomes in the GnomAD database, including 3,725 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3725 hom., cov: 31)
• Consequence: MERTK NM_006343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487
• Publications: 6 publications found

Genes affected

MERTK (HGNC:7027): (MER proto-oncogene, tyrosine kinase) This gene is a member of the MER/AXL/TYRO3 receptor kinase family and encodes a transmembrane protein with two fibronectin type-III domains, two Ig-like C2-type (immunoglobulin-like) domains, and one tyrosine kinase domain. Mutations in this gene have been associated with disruption of the retinal pigment epithelium (RPE) phagocytosis pathway and onset of autosomal recessive retinitis pigmentosa (RP). [provided by RefSeq, Jul 2008]

MERTK Gene-Disease associations (from GenCC):

• MERTK-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 38

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MERTK	NM_006343.3	c.62-8727G>T		intron_variant	Intron 1 of 18	ENST00000295408.9	NP_006334.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MERTK	ENST00000295408.9	c.62-8727G>T		intron_variant	Intron 1 of 18	1	NM_006343.3	ENSP00000295408.4
MERTK	ENST00000439966.5	n.62-8727G>T		intron_variant	Intron 1 of 18	1		ENSP00000402129.1
MERTK	ENST00000409780.5	c.-47+21597G>T		intron_variant	Intron 1 of 17	5		ENSP00000387277.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29659 AN: 151866 Hom.: 3720 Cov.: 31

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0809

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.173

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.195 AC: 29671 AN: 151984 Hom.: 3725 Cov.: 31 AF XY: 0.204 AC XY: 15151 AN XY: 74272

African (AFR) AF: 0.0539 AC: 2238 AN: 41524

American (AMR) AF: 0.255 AC: 3888 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 737 AN: 3466

East Asian (EAS) AF: 0.0807 AC: 415 AN: 5142

South Asian (SAS) AF: 0.311 AC: 1496 AN: 4812

European-Finnish (FIN) AF: 0.384 AC: 4045 AN: 10522

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16233 AN: 67940

Other (OTH) AF: 0.172 AC: 363 AN: 2108

Alfa AF: 0.132 Hom.: 294

Bravo AF: 0.177

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.19
DANN	Benign	0.47
PhyloP100		-0.49
Mutation Taster		=100/0	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: rs867311; hg19: chr2-112677970;