16-84479983-T-C

Position:

• chr16-84479983-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020947.4(MEAK7):​c.1301A>G​(p.Gln434Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000863 in 1,609,274 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (1 hom.)
• Consequence: MEAK7 NM_020947.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.687

Genes affected

MEAK7 (HGNC:29325): (MTOR associated protein, eak-7 homolog) Involved in several processes, including TOR signaling; positive regulation of protein localization to lysosome; and response to insulin. Located in cytosol; lysosomal membrane; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003116101).
• BP6: Variant 16-84479983-T-C is Benign according to our data. Variant chr16-84479983-T-C is described in ClinVar as [Benign]. Clinvar id is 707958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00493 (751/152318) while in subpopulation AFR AF= 0.0168 (697/41582). AF 95% confidence interval is 0.0157. There are 5 homozygotes in gnomad4. There are 343 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEAK7	NM_020947.4	c.1301A>G	p.Gln434Arg	missense_variant	8/8	ENST00000343629.11	NP_065998.3
MEAK7	XM_005256075.3	c.1301A>G	p.Gln434Arg	missense_variant	9/9		XP_005256132.1
MEAK7	XM_017023511.2	c.1301A>G	p.Gln434Arg	missense_variant	8/8		XP_016879000.1
MEAK7	XM_047434410.1	c.1301A>G	p.Gln434Arg	missense_variant	8/8		XP_047290366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEAK7	ENST00000343629.11	c.1301A>G	p.Gln434Arg	missense_variant	8/8	1	NM_020947.4	ENSP00000343635	P1
MEAK7	ENST00000566995.5	c.*715A>G		3_prime_UTR_variant, NMD_transcript_variant	9/9	5		ENSP00000454265
MEAK7	ENST00000570036.5	c.*1356A>G		3_prime_UTR_variant, NMD_transcript_variant	9/9	2		ENSP00000455332

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 751 AN: 152200 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00131 AC: 325 AN: 248992 Hom.: 1 AF XY: 0.000988 AC XY: 133 AN XY: 134632

Gnomad AFR exome AF: 0.0180

Gnomad AMR exome AF: 0.000705

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000437 AC: 637 AN: 1456956 Hom.: 1 Cov.: 31 AF XY: 0.000380 AC XY: 275 AN XY: 724494

Gnomad4 AFR exome AF: 0.0154

Gnomad4 AMR exome AF: 0.00106

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.000998

GnomAD4 genome AF: 0.00493 AC: 751 AN: 152318 Hom.: 5 Cov.: 32 AF XY: 0.00461 AC XY: 343 AN XY: 74480

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00101 Hom.: 4

Bravo AF: 0.00642

ESP6500AA AF: 0.0191 AC: 84

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00171 AC: 208

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000547

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.2
DANN	Benign	0.60
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.73	N
MutationTaster	Benign	0.64	D;D
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.037
Sift	Benign	0.45	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.046
MVP		0.040
MPC		0.0021
ClinPred		0.0044	T
GERP RS		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.019
gMVP		0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs36033299; hg19: chr16-84513589;